Midterm Flashcards
1
Q
What are the three basic purposes that neural systems serve?
A
1) Sensory systems report information about the state of the organism and its environment
2) Motor systems organize and generate actions
3) Associational systems provide ‘higher-order’ brain functions such as perception, attention, memory, language & thinking
2
Q
How is the Human Nervous System organized?
A
1) Central nervous system (CNS)
- Brain
- Spinal cord
2) Peripheral nervous system (PNS)
- Sensory neurons
- Somatic motor division
- Visceral/autonomic motor division
3
Q
What is the reticular theory?
A
Scientist Golgi, supported the ‘reticular theory’ that all neurons formed a single continuously connected network.
4
Q
How did Ramon y Cajal use Golgi’s method?
A
He used it to reconstruct neurons and argued for the ‘neuron doctrine’ that neurons communicate at specialized contact points rather than through physical continuity.
It was identified that these points of communication were ‘synapses.’ Ultimate proof was discovered when there was an electron microscopy to visualize synapses and confirm that neurons are discrete entities.
5
Q
What are the two basic cell types?
A
-> Neurons and glia are the primary cells of the brain
6
Q
What are the function of neurons?
A
- Process information
- Sense environmental changes
- Communicate changes to other neurons via electrical signalling
- Control bodily responses
7
Q
What are the functions of Glia?
A
- support the signalling functions of neurons
- insulate, nourish, repair neurons (probably more also)
-maintaining the ionic milieu of neurons - modulating the rate of action potential propagation
- modulating synaptic transmission by regulating neurotransmitter uptake & metabolism at the synaptic cleft
- regulating recovery from neural injury
- interface between brain & immune system
- facilitating flow of interstitial fluid through the brain during sleep
- complexes processes extending from their cell bodies but these serve different functions than neuronal processes
- Glia is Greek for ‘glue’ - long through that glia’s primary purpose was to hold neurons together
8
Q
Dendrites
A
- primary target for synaptic input from axon terminals of other neurons
- extensive branching that differs greatly between neuron types
- complexity of dendritic arbour depends on number of inputs a neuron recieves
- arbour complexity dictates capacity to integrate information from many sources
9
Q
axon
A
- signal transduction from cell body; reads out information
- most neurons have only one that extends for a long distance
- some branching
- site of output to other neurons
10
Q
action potential
A
- electrical event that carries signals
- also called ‘spikes’ or ‘units’ are ‘all or nothing’ changes in electrical potential across the neuronal cell membrane
11
Q
pre-synaptic terminal
A
where molecules are secreted into synaptic cleft
12
Q
post-synaptic specialization
A
contains receptors where molecules bind
13
Q
synaptic cleft
A
space between pre- and post-synaptic terminals
14
Q
How are neurons specialized for long-distance electrical signaling?
A
- Extensive branching:
-> dendrites
-> axons
15
Q
What happens to information conveyed by synapses on the dendrites?
A
It is integrated and converted to an electrical signal, the action potential, at the origin of the axon.
16
Q
How far does the axon extend from from the neuronal cell body?
A
- It may travel a few hundred micrometers or even further.
eg. local interneurons have very short axons
eg. axons from the human spinal cord to the foot are a meter long - axons can branch to innervate multiple post-synaptic sites on multiple neurons.
17
Q
What is the axon terminal of the presynaptic neuron immediately adjacent to?
A
- the postsynaptic area on the target cell.
18
Q
neurotransmitters
A
they are specialized molecules that are released from the presynaptic terminal, cross the synaptic cleft, and bind receptors in the postsynaptic density
19
Q
nodes of ranvier
A
gaps in the myelination of axons where action potentials are generated (regenerated)
20
Q
astrocytes
A
- type of glia
- restricted to brain & spinal cord
- major function is to maintain the appropriate chemical environment for neuronal signalling, including formation of the blood-brain barrier
- recent evidence suggests astrocytes secrete substances to influence construction of new synaptic connections
21
Q
oligodendrocytes
A
- type of glia
- restricted to brain & spinal cord
- lay down myelin around axons, regulating speed of transmission of action potentials
22
Q
schwann cells
A
- type of glia
- provide myelin in the peripheral nervous system
23
Q
microglia
A
- type of glia
- primarily scavenger cells that remove cellular debris from sites of injury or cell turnover
- secrete signalling molecules, particularly cytokines (immune signalling molecules)
24
Q
glial stem cells
A
- type of glia
- cells that retain the capacity to proliferate and generate additional precursor cells or differentiated glia or neurons
25
What is a neural circuit?
- neurons do not act alone
- diverse subsets of neurons are organized into ensembles called neural circuits that process specific types of information
- specific arrangement varies with function
26
What are basic components of neural circuits?
1) Afferent neurons carry information toward CNS
2) Efferent neurons carry information away from CNS
3) Interneurons participate in local aspects of circuit function
27
What defines all neural circuits?
- direction of information flow
28
knee-jerk response
- simple reflex circuit
1) Hammer tap stretches tendon, which in turn, stretches sensory receptors in leg extensor muscle
2) Sensory neuron synapses with and excites motor neuron in the spinal cord. Sensory neuron also excites spinal cord interneuron. Interneuron synapse inhibits motor neuron to flexor muscles.
3) Motor neuron conducts action potential to synapses on extensor muscle fibres, causing contraction. Flexor muscle relaxes because the activity if its motor neurons has been inhibited.
4) leg extends.
29
divergent circuits
spread information
one presynaptic neuron branches to affect a larger number of postsynaptic neurons
30
convergent circuits
integrate information
many presynaptic neurons converge to influence a smaller number of postsynaptic neurons
31
Electrophysiological recordings are used to study neural circuits. How?
Electrophysiological recordings:
- Classically, the primary technique for probing neural circuit function.
- > Extracellular recording:
- An electrode is placed near a neuron. Useful for detecting temporal patterns of action potential activity
-> Intracellular:
- An electrode is placed inside the neuron
- Can detect smaller, graded changes in electrical potential that trigger action potentials
- Assess communication among neurons within a circuit
32
Calcium Imaging is used to study neural circuits. How?
- record transient changes in the concentration of calcium ions that are associated with action potential firing to infer changes in neural activity.
33
Optogenetic mechanisms are used to study neural circuits. How?
- Optogenetic mechanisms can assess the physiology of neural circuits based on the activation of neuronal populations.
- Bacterial channels referred as opsins
transduce light energy into chemical signal that activates channel proteins.
34
Describe the building blocks: Neuron, Circuit & System
Diverse subsets of neurons constitute ensembles called neural circuits which are primary components of neural systems that process specific types of information.
35
sensory systems
acquire & process information from the internal and external environment
36
motor systems
respond to information (e.g sensory) by generating movements
37
association systems
lie between input & output systems
38
Neural Systems are characterized by:
-> Unity of function
- a system is defined by the neurons and connections dedicated to a function. (visual system defined by all neurons and connections dedicated to vision)
- components of a system are often distributed throughout the body and brain. (sensory systems include peripheral sensory specializations e.g. ear, eye, skin, nose) (motor systems include peripheral motor nerves and target muscles)
-> orderly representation of specific information at various levels
-> division of the function of the system into subsystems that are relayed and processes in parallel
- information from sub-modalities is processed separately but in parallel.
e.g. frequency and volume of an auditory signal, colour & motion of a visual stimulus
39
Topographic maps
- they reflect a point-to-point correspondence between the sensory periphery and neurons within the CNS
- systems that distinguish differences between neighboring points (e.g. vision, in visual field or touch, on the body's surface) represent information topographically.
40
computational maps
- systems like smell and taste use these maps to compare, assess, & integrate multiple stimulus attributes to extract essential information about stimuli
41
do the higher order systems such as language and emotion go by a specific map?
no, they are less well understood and may not follow the neat organization of sensory & motor systems.
42
nervous system
collection of neurons
43
gray matter
cell bodies in the brain, appear grey in freshly dissected brain
44
cortex
thin sheet of neurons, usually at the brain’s surface
45
nucleus
clearly distinguishable mass of neurons, usually deep in the brain (nucleus is Lain for “nut”)
46
substantia
related neurons, but with less distinct boundaries than a nucleus
47
locus
s (pl: loci): small, well-defined group of cells
48
ganglion
(pl: ganglia): collection of neurons in the PNS (ganglion is Greek for “knot”). Only the basal ganglia in the CNS.
49
nerve
a bundle of axons in the PNS. Only nerve in the CNS is the optic nerve
50
white matter
generic term for collection of axons; appear white from myelination
51
tract
collection of CNS axons having common origin and destination
52
bundle
collection of axons that run together but do not necessarily have a
common origin/destination
53
capsule
axon collection that connects cerebrum with brainstem
54
commisure
axon collection that connects one side of the brain to the other
55
lemniscus
a tract that meanders through the brain like a ribbon
56
Describe genetic analysis of neural system
- genetic variation shapes structure & function of the nervous system
- in humans, this has been studied by:
-> genetic analysis in families affected by inherited diseases
-> look for genetic variation between affected & unaffected individuals
-> genome wide associated studies (GWAS)
- once candidate genes have been identified in humans, these can be studied in cell models or animal models to understand the biological function of these genes
57
genome wide associated studies (GWAS)
Large scale population
studies that assesses
statistical correlation
between genetic variation
and frequency of
clinically diagnoses
conditions to identify ‘risk
locus’ for a particular
condition
58
describe the structural analysis of neural systems: lesion studies.
- Inferences of functional location made
by correlating post-mortem
observation of gross brain damage
with functional deficits observed in life
- e.g. Henry Molaison (HM) lost the
ability to form new lasting
autobiographical memory.
- Inherent limitations include
-> Biased recall of functional changes
-> Uncontrolled damage
- Animal studies experimentally induce
lesions but still limited
59
What does tract tracing permit?
- detailed assessment of connections
between brain regions
-> retrograde (cells that send connections to the injection site)
-> anterograde (regions that receive connections from the injection site)
60
Historically, what were the most widely used methods to do functional analysis of neural systems?
- electrophysiological recording
- functional brain imaging
61
what are non-inasive techniques of functional analysis of neural systems?
- EEG
- transcranial magnetic stimulation
- CT
- fMRI
62
Anatomical references for humans
rostral = forehead
caudal = back of head
dorsal = top of brain
ventral = bottom of brain
superior = above head
inferior = below
anterior = in front of
posterior = behind
For the brain stem & spinal cord:
- dorsal is to the back
- rostral is towards the top of the head
For the forebrain:
- dorsal is toward the top of the head
- rostral is towards the face
63
What are the 3 different planes when cutting the brain?
1) Sagittal
2) Horizontal (axial)
3) Coronal (frontal)
When we cut the brain along the midline, we observe the brain has bilateral symmetry.
64
contralateral
on opposite sides of the midline
65
ipsilateral
on the same side of the midline
66
What are the 7 basic parts that the CNS has?
* Spinal cord
* Medulla
* Pons
* Midbrain
* Cerebellum
* Diencephalon
* Cerebrum
67
brainstem
- medulla
- pons
- midbrain
68
forebrain
diencephalon and cerebral hemispheres (cerebrum)
69
cerebrum
generally receives and sends information to the contralateral
side of the body
70
cerebellum
* ‘tiny brain’
* contains as many neurons as cerebrum
* Movement control
71
brain stem
* Relay between cerebrum/cerebellum and spinal cord
* Basic vital functions e.g. breathing
72
Describe the spinal cord - external anatomy
-> peripheral nerves that innervate much of the body arise from the spinal nerves
-> sensory information carried by afferent axons of the spinal nerves enters the cord via the dorsal roots
-> motor commands carried by the efferent axons leave the spinal cord via the ventral roots
-> once the dorsal and ventral roots join sensory and motor axons usually travel together in the spinal nerves
73
Describe the spinal cord - Internal Anatomy
- Interior of the cord is formed by gray matter, surrounded by white matter
- cervical and lumbosacral enlargements accommodate the greater number of nerve cells and connections required to process information from upper and lower limbs
- the white matter of the spinal cord is divided into dorsal, lateral and ventral columns
- dorsal columns carry ascending sensory information from somatic mechanoreceptors
- lateral columns include axons that travel from the cerebral cortex to interneurons and motor neurons in the ventral horns ('lateral corticospinal tract')
- ventral columns carry both ascending information about pain & temperature, and descending motor information from the brainstem & motor cortex
- In transverse sections we can identify the dorsal and ventral horns in the gray matter
- neurons of the dorsal horns receive sensory information that enters via the dorsal roots of the spinal nerves
- the ventral horns contain cell bodies of motor neurons that send axons via the ventral roots of spinal nerves to striated muscles
74
Brainstem & Cranial Nerves
- Midbrain, pons, medulla
- located between diencephalon and spinal cord
75
What are the 3 fundamental functions of the brainstem?
- target and source for cranial nerves that deal with sensory and motor function of head and neck
- A 'throughway' for ascending sensory tracts from spinal cord, sensory tracts for head and neck, descending motor tracts from forebrain, local pathways linking eye movement centers.
- regulating levels of consciousness through extensive forebrain projections.
76
are brainstem structures tightly packed
yes
77
what are cranial nerve nuclei in the brainstem a target of
they are the target of cranial sensory nerves and the source of cranial motor nerves
78
what is there a seperation of in the brainstem?
- there is a separation of sensory & motor nuclei in the brainstem
- sensory nuclei are found laterally
- motor nuclei are found medially
79
what does the lateral fissure separate?
temporal lobe from frontal & parietal lobe
80
what does the central sulcus separate
frontal and parietal lobes
81
what does the parieto-occipital sulcus seperate
parietal and occipital
82
what does the precentral gyrus locate
motor cortex
83
what does the postcentral gyrus locate
somatic sensory cortex
84
what is the insula cortex hidden beneath
frontal and temporal lobes
85
corpus callosum
bridges the two hemispheres, carrying axons originating from neurons in cerebral cortex of each hemisphere to contact target neurons in the opposite cortical region
86
what does the calcarine sulcus locate
the primary visual cortex
87
what is the cingulate gyrus part of
the limbic system
88
what are the components of diencephalon
thalamus
hypothalamus
89
thalamus
- relay of sensory and motor signal to relevant primary cortical cortex and also distributer of high order signals from one part of cortical area to another
- the sensory pathways from the eye, ear, and skin all relay in the thalamus before terminating in the cerebral cortex
- around 50 subdivisions maintain distinct inputs & outputs
- receives input from throughout brain and spinal cord
- sends axons to different cortical areas
- sends information back to brain stem via internal capsule and basal ganglia
90
hypothalamus
homeostatic and reproductive functions
91
where is the amygdala located
infront of the hippocampus
92
What are the parts of the basal ganglia
caudate, putamen & globus pallidus
93
what does the anterior commissure axon tract connect
it connects the two hemispheres
94
what is the internal capsule
major pathway linking cerebral cortex to brain & spinal cord
95
what does damage to major blood vessels by trauma or stoke result in
combinations of functional defects caused by local cell death, disruption of axons passing through area of vascular damage.
96
what are neruons highly sensitive to?
oxygen (& glucose) deprivation because they have high metabolic rate
97
What does brief loss of blood suply (ischemia) caue
cellular changes that may end in cell death
98
what does prolonged loss of blood supply lead to
cell death and degeneration
99
stroke
the death or dysfunction of brain tissue that follows compromised blood supply
100
What is the blood-brain barrier? (BBB)
- BBB protects the brain from toxins & fluctuations in ionic milieu
- Interface between walls of capillaries and surrounding tissue are observed throughout the body
- In the brain, tight junctions form between capillary endothelial cells that are not seen elsewhere in the body
101
How do molecules enter the brain?
They must move through endothelial membranes:
- lipid soluble
- Actively transported e.g. glucose
102
Meninges
- Greek for "covering"
- membranes protecting the brain and spinal cord preventing direct contact with skull or bone
103
dura mater
outermost, latin for "hard mother"
104
Arachnoid membrane
- middle layer with a web-like consistency, from the Greek for "spider"
- blood vessels pass between the dura and arachnoid membranes-ruptures to these subdural hematomas
-fluid build-up here is dangerous because is puts pressure on the CNS
105
pia mater
- inner layer
- adheres closely to the brain and included many blood vessels, latin for "gentle mother"
- the pia is separated from the arachnoid by the subarachnoid space which contains cerebrospinal fluid (CSF)
106
ventricular system
- ventricles are canals through the brain filled with cerebrospinal fluid (CSF)
- provide useful anatomical landmarks in the brain
107
what is CSF produced by? where does it flow?
- produced by the choroid plexus, special tissue lining the ventricles of the brain
-> produces 500 mL CSF/day
-> normal volume in ventricular system is 150 mL
-> CSF turnover multiple times daily
- CSF flows through the ventricles and exits the CNS into the subarachnoid space by small openings along the dorsal midline of the forebrain, where it is absorbed by subarachnoid vilii into the blood
108
glymphatic system of the brain
* The brains waste clearance system
* CSF passes from arterial perivascular
space through the substance of the
brain
* The CSF rinses metabolic waste and
discarded proteins
* The waste-carrying CSF passes out of
the brain via the perivascular space
surrounding veins
* CSF flow increases during sleep when
extracellular spaces expand
109
Sensation
Sensation entails the ability to transduce, encode, and ultimately perceive information generated by stimuli arising from both external and internal environments.
110
What are the 5 basic senses
1) Somatic - pressure, temperature, vibration and pain
2) Vision - light waves
3) Audition - sound waves
4) Taste - chemical
5) Smell or Chemical sense
111
What is the sixth sense
proprioception (sense of where your body is)
112
All senses provide very different information. But they follow similar basic rules for sensation. What are they?
- specialized cells (receptors) covert energy (mechanical forces - light) into afferent sensory signals - conveys information to the brain.
- signals convey information about:
Modality (touch versus pain: type of touch - sharp versus dull)
where it is (location)
intensity
time course
113
Why is understanding deficits in sensory processing very important?
Diagnosing various neurological problems
114
What is the function of the somatic sensory system?
Mediates a range of sensations e.g. touch, pressure, limb position, temperature, pain
115
what are the three sub-systems of the somatic sensory system?
1) fine touch, vibration, pressure
- cutaneous mechanoreceptors
2) Proprioception: sense of relative position of our body parts in space
- specialized receptors associated with muscles, tendons & joints
3) Temperature, pain and non-discriminative (sensual) touch
116
Transmission of somatic sensory information
1) Receptors (nerve endings) in skin/muscles/joints
2) Afferent nerve fiber (axons)
3) Afferent cell body (dorsal root ganglia or cranial nerve ganglia-trigeminal ganglia)
4) Central nervous system circuits
117
What is the external anatomy of the spinal cord?
- the peripheral nerves that innervate much of the body arise from the spinal nerves (sensory - afferent AND motor - efferent)
- sensory information carried by afferent axons of the spinal nerves enters the cord via the dorsal roots
118
Where are cell bodies of afferent nerve fibres located?
- in the ganglia adjacent to the spinal cord & brain stem
dorsal root ganglia: body
trigeminal ganglia : head
119
What is a characteristic of neurons of dorsal root ganglia?
they are pseudounipolar - no synapse before entering the spinal cord
120
where is the first synaptic terminals?
within the grey matter of the spinal cord
121
what does the PNS neurons supply the CNS with?
information about sensory events in the periphery
122
'Pseudounipoalr' sensory neurons vs bipolar neurons
- Bipolar neuron (axon, dendrites)
- pseudounipolar neurons
-> one axon with two branches, no true dendrites
central: cell body to spinal cord
peripheral: cell body to peirphery
123
where are 'pseudounipolar' sensory neurons found?
- they are found in the dorsal root ganglia:
cell body in DRG
Axon exits DRG, splits into 2 branches
Central branch to dorsal horn of spinal cord 'peripheral branch travels through the spinal nerve to skin, join, muscle
also found in sensory ganglia of cranial nerves
124
How does sensory transduction convert energy from a stimulus into an electrical signal?
1) sensory stimulus produces a depolarization current in the afferent nerve endings called a receptor potential
2) upon reaching a threshold, action potentials are generated in the afferent fibre
3) APs then travel along the peripheral axon past the cell body in the dorsal root ganglion & along the central axon to reach the synaptic terminals in spinal cord
125
What are some characteristics of afferent fiber terminals? what can they be?
They can be:
- encapsulated by specialized receptor cells 'mechanoreceptors' which usually tune in to a particular feature, or lower threshold - more sensitive
126
What are free terminals (pain)?
- higher threshold
- same stimuli in higher intensities will produce 'pain'
127
How is a 'receptor potential' (depolarizing current) generated?
- a stimulis (physical) changes the permeability of cation channels in the afferent nerve endings
(the same basic mechanisms mediate sensory transduction in all somatic sensory efferents)
128
Explain: sensory transduction: converting physical stimuli to electrical signals.
- if the stimulus is sufficient, the receptor potential reaches the threshold to generate an action potential in the afferent fiber
- the rate of action potential firing is proportional to the magnitude of depolarisation
- because somatic sensory neurons are pseudounipolar, the electrical activity does not need to be conducted through the cell body membrane, but rather travels along the continuous peripheral and central axon
129
What are piezo mechanotransduction channels?
Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels
130
What do distinct functional properties of somatic sensory afferents define?
distinct classes of afferents with specialized mechanoreceptors which convey unique sensory information
131
what are sensory afferents often encapsulated by?
specialized receptor cells that tune the fibre to specific stimulation
132
are free nerve endings important in pain sensation?
yes
133
What are for key properties characterize sensory afferents?
- axon diameter
- receptive field
- temporal dynamics
- quality of somatic sensory stimulation
134
what does axon diameter determine?
conduction speed of conduction of action potential (larger, faster)
135
What is the receptive field of sensory afferent?
It is the area of skin surface which stimulation results in a significant change in the rate of action potentials
136
does receptive field size vary in different parts of the body?
yes
137
what is the size of the receptive field largely determined by?
- the branching of the sensory afferents in the skin: smaller arborization -> smaller receptive field
- density of afferent innervation, more afferents -> smaller receptive field
138
what does receptive field size determine?
- spatial accuracy with which tactile stimulaiton can be sensed
- two point discrimination measures the minimum distance between two simultaneously applied stimuli that is perceived as two distinct stimuli
- discrimination varies dramatically
fingertips: 2 mm
forearm: 40 mm
139
What is the two-point discrimination threshold?
- two-point discrimination varies throughout the body
- somatic acuity is much higher in fingers, toes and face than in arms, legs, toso
- this is the result of differences in receptive field size
- species specific
140
How do temporal dynamics affect sensory afferents?
- sensory afferents respond to the same stimulus with different temporal dynamics
- rapidly adapting afferents: fire upon the initiation of stimulation, quickly become quiescent if stimulation is maintained, may fire again on termination
- slowly adapting efferents continue to fire with sustained stimulation
- rapidly adapting afferents may be important for conveying information about changes in ongoing stimulation e.g. movement
- slowly adapting afferents may convey information about spatial attributes of a stimulus e.g. size, shape
- adaptation characteristics are determined in parts by properties of mechanoreceptors
141
Different classes of sensory afferents respond only to a restricted set of sitmuli. e.g. stretch, temperature. what is this determined by?
This is determined by:
differences in properties of channels
filter properties of mechanoreceptors
these different afferents are parallel pathways and remain segregated (even if they travel together at first)
142
What are the three sub-systems of the somatic sensory system?
fine touch, vibration, pressure
cutaneous mechanoreceptors
143
proprioception
sense of relative position of our body parts in space, specialized receptors associated with muscles, tendons & joints
144
Touch/cutaneous sensation
best understood for glabrous skin (i.e. palm, fingertrips) - specialized for high- definition neural image of manipulated objects.
depends on specialized end organs surrounding the nerve terminal: mechanoreceptors
145
haptics
active touching - interpretation of complex spatiotemporal patterns of stimuli - active many classes of mechanoreceptors
146
stegnosis
capacity to identify an object by manipulating it with the hand
147
Experiments recording from individual sensory afferents in nerves have identified the specific contributions of 4 distinct mechanoreceptors to somatic sensation. What are they?
1) Merkel cell-neurite complex
2) Meissner corpuscle
3) Pacinian corpuscle
4) Ruffini corpuscle
148
What is a mechanoreceptor?
it is a receptor that provides an organism with information about mechanical changes in its environment. virtually all mechanoreceptors have specialized end organs surrounding the nerve terminal.
149
mechanoreceptor afferents for touch: what is the sensitivity to mechanical displacement a property of?
the sensitivity to a mechanical displacement is a property of both the nerve terminal membrane and the specialized capsule
150
Merkel's disks (aka merkel cell-neurite complex)
a merkel cell (a specialized epithelial cell) closely associated with an enlarged nerve terminal
151
meissner's corpuscles
globluar, fluid-filled structure that encloses a stack or flattened epithelial cells; the sensory nerve terminal is entwined between the various layers
152
ruffini endings
nerve fibers that are often but not always associated with a fibrous capsule
153
pacinian's corpuscles
consists of many modified fibroblasts to make lamellae like an onion
each is connected to a sensory neuron
154
merkel cell afferents
- slow adapting - static aspect of touch 25% of mechanosensory afferents in hand
- highest spatial resolution of all sensory afferents
- enriched in fingertips
- from merkel cells and the sensory afferents express Piezo2
- highly sensitive to points, edges, and curvature and suited to processing information about form & texture
- often afferents sampling information from the epidermis
155
meissner afferents
- express Piezo2
- rapidly adapting
- high spatial resolution
- 40% of mechanosensors in hand
- skin indentation deforms the corpuscle to trigger receptor potentials
- removal of stimulus relaxes the corpuscle to resting position also generating receptor potentials
- meissner corpuscles are formed by a connective tissue capsule of flattened cells derived from schwann cells with the center of each capsulse containing 2-6 afferent nerve fibres
156
what is the difference of meissner afferents to merkle?
- they are closer to the skin surface
- more sensitive to skin deformation
- larger receptive field -> reduced spatial resolution
- sensitive to vibration of objects moving across skin
- detect slippage between the skin and the object held in hand, essential feedback information for the efficient control of grip.
157
pacinian afferents
- rapidly adapting
- 10-15% of mechnosensors in hand
- pacinian corpuscles located deep in dermis or subcutaneous tissue. concentric layers of membranes around a single fiber (like an onion)
- laminar structure of pacinian corpuscle filters out all but high frequencies.
- lower response threshold tha meissner corpuscles
- can respond to skin displacements as small as 10 nm
- large receptive fields
- detect vibrations transmitted through objects in touch with the hand
- may be important in tool use
158
ruffini afferents
- slow adapting
- 20% of mechanoreceptors in hand
- ruffini corpuscles are elongated, spindle-shaped capsules in dermis and also found in ligaments and tendons
- long axis of corpuscle lies parallel to stretch lines in skin making them sensitive to cutaneous stretching with digit or limb movement
- contribute, along with muscle receptors to sensation of finger position and hand conformation
159
The different kinds of information that sensory afferents conveyed to central structures was first illustrated in?
Experiments conducted by K. O Johnson and colleagues, who compared the responses of different afferents as a fingertip was moved across a row of raised brailled letters
160
Proprioception
- information about mechanical forces arising within the body itself.
- proprioceptors (low threshold mechanoreceptors) provide continuous detailed information about the position of the limbs and other body parts in space
-> muscle spindle, gogli tendon organ, joint receptors
- essential for accurate performance of complex movements
- in the case of position of the head, integration with vestibular system.
161
muscle spindles
- found in striated (skeletal) muscle
- consist of 4-8 specialized intrafusal muscle fibers surrounded by capsule of connective tissue, distributed in parallel with extrafusal fibers
- sensory afferents coil around the centra part of the intrafusal spindle. when the muscle is stretched, tension of intrafusal fibers activates mechanically gated ion channels, triggering action potentials.
162
muscle spindle is innervated by?
two types of fibers:
1) primary endings
2) secondary endings
also innervated by efferent y motor neurons in the ventral horn of the spinal cord, which change intrafusal fiber tension and increase sensitivity of the afferents to changes in muscles length.
163
primary endings that innervate muscle spindles
- group Ia afferents (largest myelinated sensory axons)
- rapidly adapting responses to changes in muscle length
- transmit information about limb dynamics
164
secondary endings that innervate muscle spindles
- group II afferents
- sustained responses to constant muscle lengths
- information about static limb position
165
How does density of spindles in human muscle vary with function?
- muscles that generate coarse movement have fewer spindles than muscles that generate very fine movements
- more precise movement requires more refined sensory input (eyes, hand, neck)
166
artificial stimulation of spindles by vibration produces..?
- sensory illusions of altered limb position in stationary limbs
- illusion only produced if visual input is prevented
- in normal conditions, properioception is achieved by integration of somatic and visual cues
167
what does joint angle perception arise from?
from integration of afferent signals from muscle spindles and efferent motor commands
168
golgi tendon organs
- low-threshold mechanoreceptors in tendons
- senses changes in muscle tension
- distributed along collagen fibers that form tendons
- arranged in series with extrafusal muscle fibers
- innervated by branches of group Ib afferents
- contribute less to conscious sensation of muscle activity
- important role in reflex circuits protecting muscle from injury
169
what central pathways convey tactile information?
- tactile afferents, enter through dorsal horn of spinal cord
- the main ascending branches (direct projections) extend ipsilaterally through the dorsal columns (also called the posterior funiculi) of the cord to the lower medulla, where they synapse on neurons in the dorsal column nuclei.
170
what central pathways convey proprioceptive information?
- proprioceptive afferents enter through dorsal horn of spinal cords
- many fibres then bifurcate to form both ascending and descending branches, collaterals synapse on neurons of the dorsal and ventral horn
- proprioceptive information also reaches cerebellum where it is required in control of voluntary movement
171
Spinocerebellar tract
first order neuron collaterals from lower body synapse in Clarke's nucleus. Neurons in Clarke's nucleus send their axons via the dorsal spinocerebellar tract to the cerebellum, with a collateral to the dorsal column nuclei.
172
where do the proprioceptive afferents for the upper body ascend via?
via the dorsal column to the dorsal column nuclei; the cuneate nucleus, in turn, relays signals to the cerebellum.
173
Compare the central pathways for conveying proprioceptive and tactile information? (first order neuron - ipsilateral)
Proprioceptive:
Dorsal Root ganglion / Trigeminal ganglion
Tactile:
Dorsal column (ascend ipsilaterally) Cuneatus,
gracile tracts //Trigeminal trac
174
Compare the central pathways for conveying proprioceptive and tactile information? (second order neuron - ipsilateral)
Proprioceptive:
Gracile, Cuneiform nuclei / Trigeminal nucleus
Tactile:
Medial Lemniscus // Trigeminal Lemniscus **Axons
cross the midline
175
Compare the central pathways for conveying proprioceptive and tactile information? (third order neuron - contralateral)
Proprioceptive:
Ventral posterior complex / Medial Thalamic and
Parabrachial (nuclei in the thalamus)
Tactile:
Internal capsule
176
Central pathway conveying proprioceptive and tactile information (cerebral cortex)
Cerebral cortex – Primary somatosensory cortex
– postcentral gyrus – parietal lobe // Anterior
cingulate and insula. Also, secondary
somatosensory cortex.
177
somatic sensory in the thalamus
- ascending somatic sensory pathways from the spinal cord and brainstem converge in the ventral posterior complex of the thalamus in a highly organized manner
- afferents terminate in somatotopic representation of the body and head
-> VP lateral: relay from body (via medial lemniscus)
-> VP medial: relays from face (via trigeminal lemniscus)
- parallel pathways (body and head)
- inputs carrying different types of somato-sensory information terminate on seperate populations of relay cells
- information from distinct somatosensory receptor types remains segregated in passage to cortex
178
where do most neurons from VP thalamus project?
- to layer 4 of primary somatic sensory cortex (SI)
- SI is located in post central gyrus of the paritetal lobe and has 4 regions (brodmann's area 3a, 3b, 1 and 2)
- each region contains a complete somatotopic map of the body in a medial to lateral arrangement
179
somatotopic maps in SI
- foot, leg, trunk, forelimbs and face are represented in a medial to lateral arrangement
- do not represent the body in its actual proportions
-> bigger area (and number of neurons) for more richly innervated regions
-> homunculus - grossly enlarged representation of face & hands
- the proportionality of representation reflects the neural circuitry required to govern the associated functions (e.g. facial expressions, speech, manual manipulation of objects)
180
for a somatopic map for a naked mole rate what dominates?
the teeth
181
Despite similar topography
across SI areas, functional
properties of neurons in each
region are distinct, reflecting
segregated, parallel inputs
from VP thalamus. What do neurons in 3b &1, 3a, and 2 respond to?
3b & 1: respond primarily to cutaneous stimulation
3a: respond primarily to proprioceptive stimulation
2: respond to both tactile & proprioceptive stimuli
182
What is an example of neurons in SI forming functionally distinct columns?
- For example, neurons with
responses to rapidly and slowly
adapting mechanoreceptors
cluster into separate zones
within the representation of a
single finger
- This modular organization is a
fundamental feature of cortical
organization but the functional
significance is still being
determined
183
describe the functional hierachy with 3b as an obligatory first step in cortical processing
- 3b receives largest input from VP
thalamus & sends dense projections
to 1 & 2
- Lesions of area 3b in non-human
primates - deficits in all forms of
tactile sensations mediated by
cutaneous mechanoreceptors
- lesions limited to areas 1 or 2 -
partial deficits to discriminate either
the texture of objects (area 1 deficit)
or the size and shape of objects
(area 2 deficit)
184
What are substantial connections between SI areas called?
corticocortial connections
185
all regions of SI project to?
secondary somatosensory cortex
also projections to pariteal areas for motron integration & limbic areas for learning and memory
186
SII sends projections to?
limbic structures such as the amygdala and hippocampus - tactile learning and memory
187
where does SI project to?
parietal areas 5a and 7b
these areas supply inputs to neurons in the motor and premotor areas of the frontal lobe.
thats how proprioceptive afferents signalling the current state of muscle contraction gains access to circuits that initiate voluntary movements - sensorimotor integration.
188
do descending projections outnumber ascending projections?
yes
descending projections to thalamus, brainstem & spinal cord
their function is not well understood but assumed they modulate sensory information flow in thalamus and brainstem
189
plasticity in the adult cerebral cortex
- Primary somatosensory cortex
responses adapt to differences in
stimulation
-Lesioning an input
-> Initial lack of response in
corresponding cortical area
-> Gradual increase in responding to
stimulation of neighboring regions
- Changes in cortical
representation also induced
by less drastic changes in
sensory or motor
experience
--> e.g. Training a monkey to
use specific fingers to
perform a task expands
associated cortical
representation
--> e.g. local anesthetic induces
temporary remapping of
receptive fields
--> Rapid plasticity suggests
likely reflect changes in
synaptic strength of existing
synapses
190
What is sound?
- pressure waves generated by vibrating air molecules
- like ripples spreading across water but in 3D
191
what are the 4 features of sound?
- amplitude (dB: loudness)
- frequency (Hz; pitch)
- waveform (amplitude across time)
- phase
192
what is sound?
displacements of air molecules
- condensation
-rarefraction
193
what is example of complex sounds?
- birdsong and speech contain highly periodic elements
- can be modeled as the sum of sinusoidal waves of varying amplitudes, frequencies and phases
- environmental sounds e.g. wind lack periodic structure
194
fourier transform
- decomposes a function of time in its constituent frequencies - inner ear
195
the audible spectrum
- species specific:
different species emphasize the frequency of their vocalizations
also, echolocation (high frequency), predation (low frequency)
humans: 20Hz to 20kHz
loss of high frequency with age (max 15-17kHz adult)
196
auditory function
- auditory system transforms sound (air vibration patterns) into neural activity (mechanoelectric transduction)
- external and middle ears collect and amplify sound waves and transmit to the fluid-filled choclea of the inner ear
- in the inner ear, biomechanical processes allow hair cells transduce frequency, amplitude and phase of the signal into electrical signals
- acoustical decomposition results in systematic representation of sound frequency along the length of the cochlea (tonotopy)
197
What is the anatomy of the external ear?
- Pinna
- Concha
- Auditory meatus
198
what is the function of the auditory meatus?
gathers sound energy and focuses it on the tympanic membrane (ear drum)
199
what is the function of the pinna & concha?
filter differ sound frequencies to provide cues about elevation of sound source
200
what does the human auditory meatus selective boost?
it boosts sound pressure 30-100x for frequencies around 3kHz which is directly related to speech perception
201
what is the function of the middle ear?
- Boosts the pressure of the
sound's energy from the
tympanic membrane to the inner
ear by ~200x
- This is necessary to carry
airborne sound (low-impedance) to aqueous environment of inner
ear (high-impedance)
- Impedance describes a medium’s
(i.e. air, water) resistance to
movement
202
In the middle ear, how many mechanical processes boost pressure?
- two mechanical processes
- focus force from the large surface tympanic membrane to small diameter of the oval window (where bones connect to inner ear)
- level action of the ossicles:
malleus, incus, stapes
small interconnected bones
203
what is efficiency of sound transmission in the inner ear regulated by?
- the tensor tympani & stapedius muscles innervated by cranial nerve V and VII
- in response to loud noise, these muscles contract to counteract the movement of the ossicles and limit transmission of sound energy.
-> paralysis of these muscles - bell's pasly - can generate hyperacusis.
204
sensory transduction
The cochlea transforms sonically
generated pressure waves into
neural impulses carried by the
auditory nerve
( inner ear)
205
mechanical
frequency analyzer
- inner ear
- decomposing acoustical
waveforms into their elements -
tonotopy
206
what is the structure of the inner ear
- The cochlea is a small
coiled tube structure
(like a snail shell)
- Oval window & round
window are at the basal
end of the tube
207
describe the cochlea in cross-section
- Cochlear partition runs from basal
end almost to apex
- A flexible structure that supports the
basilar membrane & tectorial
membrane
- Fluid-filled (perilymph) chambers
on either side of the partition n Scala vestibuli
-> Scala tympani
-> Scala media runs within the partition
- Cochlear partition runs from basal
end almost to apex – opens at
helicotrema where scala vestibuli
and scala tympani join
208
what is the effect of the siffness of the basilar membrane along the length
making it differentially
sensitive to different
frequencies (Tonotopy)
Travelling wave in cochlea
growing in amplitude until a
point of maximum
displacement. Basilar
membrane is tuned to high
frequencies while apex
tuned to low frequencies.
209
where are hair cells located?
- located between basilar membrane and tectorial membranes: sound wave, transmitted through oval window, causes motion between these two membranes
- hair cells have 'stereocilia'
- inner hair cells receive afferents from cranial nerve VIII - carry the impulses towards the CNS
- outer hair cells receive mostly efferent innervation - amplifier/otoacoustic emmsions
210
In hair cells, which ones are the sensory receptors?
inner hair cells
211
hair cells
are epithelial cells with a bundle of hair-like processes that protrude into the scala media
each bundle has 30 to a few hundred stereocilia
212
what are tip-links of hair cells
connect the tips of
adjacent stereocilia & translate hair
bundle movement into a receptor potential
213
what strecthes the tip links?
- displacement of the hair bundle in the direction of the tallest stereocilia (kinocilium) stretches the tip-links
- this directly opens cation-selective channels that are located at the end of the link, allowing K+ to enter
- this depolarizes the hair cell
214
what does depolarization of the hair cell lead to?
- opening of voltage-gated
Ca2+ channels
- Ca2+ influx
- Neurotransmitter release
onto auditory nerve
endings
215
what compresses the tip-links?
Movement in the opposite
direction compresses the tip- links, closes the channels and
hyperpolarizes the cell
Because some channels are
open at rest, the receptor
potential is biphasic
216
describe the mechanoelectrical transduction of sound waves:
1) movement of the stereocilia back and forth modulate ionic flow to produce a graded receptor potential
2) transmitter release triggers action potential in CN VIII following the up and down vibration of the basilar membrane
- hair transduction is fast and sensitive - 10 microseconds - essential for sound localization
217
when is mechanical gating of ion channels essential?
for rapid high-resolution signal of hair cell transduction of sound waves
218
what happens if there is damage to steriocilia? (high intensity sounds)
leads
to irreversible hearing loss
219
what happens if there is damage to tip-links?
leads to temporary hearing loss as tip links can regenerate within hours
220
hair cell receptor potentials follow mechanical displacement of?
- of the hair bundle
- The hair cell can
produce a sinusoidal
wave in response to
low frequency
(<3Khz) sinusoidal
stimulation
221
at high frequencies, what does the hair cell respond with?
- direct current offset but does not faithfully track the frequency
222
What is the distribution of lower motor neurons in the spinal cord?
Each lower motor neuron innervates muscle fibers within a single muscle (all motorneurons innervating a single muscle called motor neuron pool for that muscle)
distribution of lower motor neurons are spatially distinct according to the muscle innervation in the human. motor neuron pools innervate the arm and leg.
223
how are lower motor neuron pools organized somatotopically?
DIAGRAM
224
For somatotopic connections of local circuit neurons in the spinal cord, what are the characteristics of long-distance local circuit neurons?
- located in the medial ventral horn (red axons),
- control axial muscles
- long distance and bilateral
- control the position of the body and locomotion
225
For somatotopic connections of local circuit neurons in the spinal cord, what are the characteristics of short-distance local circuit neurons?
- located in the lateral ventral horn
- control distal limbs
- short distance & unilateral
- mediate fine control of distal limb muscles
226
what are the types of lower motor neurons in the ventral horn motor neuron pools?
alpha and gamma neurons
227
what are the characteristics of gamma neurons (lower motor neurons) in the ventral horn motor neuron pools?
- small diameter
- innervate specialized
muscle fibers (muscle
spindles)
- Sensory receptors
embedded in capsules
(fusal) intrafusal
- Send sensory information
about muscle length and
speed of change in length.
228
what are the characteristics of alpha neurons (lower motor neurons) in the ventral horn motor neuron pools?
- large diameter
- innervate extrafusal muscle
fibers.
- In striated muscles generate
force for posture and
movement.
- each neuron branches widely to
terminate on 10 to 1000
individual muscle fibers whose
contraction it controls.
229
what is the ensemble of alpha MN and the muscle fibers that it innervates called?
motor unit!
muscle fibers within a motor unit are spatially distributed within the target muscle.
other alpha MNs innervating the same skeletal muscle clustered within the same motor nucleus in the ventral spinal cord.
230
does size matter in terms of motor neurons?
size does matter!
small alpha motor neurons innervate few muscle fibers forming small motor units that generate small force
large alpha motor neurons innervate larger, more powerful motor units, with greater force
231
what are the three different types of motor units?
1) Slow motor units (S)
2) Intermediate alpha motor neurons (FR)
3) Fast-fatigable motor units (FF)
232
Slow motor units (S)
are red rich in
myoglobin and mitochondria and are
resistant to fatigue, important for
sustained muscular activation –
upright posture.
233
intermediate alpha motor neurons (FR)
innervate more moderate muscle
fibers, with greater force than slow
but less than Fast motor units.
234
fast-fatigable motor units (FF)
easily fatigued, pale, low
mitochondria, motor units are
important for forceful movements like
running.
235
What is the size principle when it comes to motor units?
- In most muscles, small, slow motor
units have lower thresholds for
activation than do larger units
- Small motor units are tonically active
during activities requiring sustained
effort (e.g. standing)
- Thresholds for large, fast motor units
are only achieved during high force,
rapid movements
236
motor unit plasticity
The ability to acquire
new motor skills
depends on upper
motor neurons and
motor units
237
where does chronic electrical stimulation alter motor units?
at both level of muscle fibers and motor neuron phenotype
238
When you increase the activity of axons that stimulate a pool of motor neurons, what does this progressively increase?
increases the muscle tension of the
corresponding muscle
239
increasing tension reflects progressive recruitment of motor unit types, according to their size. In what case is which recruited?
S motor units
FR motor units
FF motor units
More stimulation, recruitment of larger, higher threshold motor units, more force.
240
the size principle
a simple solution to the problem of grading muscle force
241
Regulating muscle force: motor neuron recruitment in the cat medial gastrocnemius muscle force. How much force does standing require, walking, and when is full force used?
1) Standing requires very little
force (~ 5%) from the muscle
tendon. This is provided by the
S motor units.
2) Walking requires more force
(~25%). This is provided by
additional recruitment of FR
motor units
3) Full force is only required for
rare movements like galloping &
jumping. Maximal force is
provided by additional
recruitment of FF motor units
242
When regulating muscle force, and seeing the effect of motor neuron stimulation rate on muscle tention, when do you see a twich, unfused tetanus, and fused tetanus?
1) A twitch is a single
contraction produced
by an action potential
within the muscle fiber
itself
2) Unfused tetanus
motor neurons fire at
high frequency but
individual twitches
are apparent
3) Fused tetanus highest rate
of firing individual twitches
are indistinguishable,
sustained contraction
without relaxation
goes from low frequency at single muscle twitch (5 hz) to unfused tetanus (80Hz) to fused tetanus (100Hz)
243
under normal conditions, what does unfused tetanus achieve?
smooth movements because asynchronous firing of different lower
motor neurons provides steady input to the muscle, averaging
out changes in tension from individual muscle units
244
The number of active motor units and their rate of firing both increase with?
voluntary force
245
what are the two basic types of muscle fibers in skeletal muscle?
1) Extrafusal fibers
2) Intrafusal fibers
246
Extrafusal fibers
Large diameter muscle fibers which produce movement via the large diameter axon a motor system.
247
Intrafusal fibers
- Small diameter muscle fibers which are much shorter than extrafusal fibers. gamma motor neurons innervate intrafusal fibers to regulate muscle length at all times.
- 8-10 intrafusal fibers are grouped together in a connective tissue capsule known as the muscle spindle.
- The spindle is mechanically in parallel to the extrafusal muscle fibers.
- Intrafusal muscle fibers stretch on extension and shorten on muscle flexion.
248
what are the two types of intrafusal muscle fibers?
1) nuclear chain
2) bag
249
how many bags to chain fibres in muscle spindles?
Each muscle spindle has 2-3
bag to 4-6 chain fibers.
250
large diameter sensory axons relay rapid action potentials in response to?
stretch of the intrafusal muscle fibers.
251
What are the two types of stretch receptors in muscle spindles?
1) Spindle primary endings, group
Ia sensory afferents spiral up
bag and chain fibers, & respond
phasically to small stretches
(dynamic).
2) Spindle secondary endings,
group II sensory afferents
mainly on chain fibers, fire
tonically, proportional to stretch
(static).
252
difference between Ia and II afferents. what is mediated through the system of them?
- Ia afferent fibers form mono- and polysynaptic excitatory connections on alpha MNs.
- II afferents form polysynaptic excitatory
connections on a MNs.
- The stretch reflex is mediated through this
system.
253
Describe the motor innervation of the spindle
The muscle spindle is innervated by two
types of g axon: dynamic and static.
The dynamic axon terminates on dynamic bag intrafusal fibers and the static axon terminates on static bag and chain fibers.
The dynamic bag intrafusal fiber is
innervated by one or two dynamic axons.
254
What is the simplest motor reflex?
stretch reflex
255
how does stretch reflex work?
Stretching a muscle spindle
leads to increased activity in
group Ia sensory afferents and
an increase in the activity of a
motor neurons that innervate
the same muscle.
A unique monosynaptic reflex.
Group Ia sensory afferents also directly
excite the motor neurons that innervate
synergistic muscles, and indirectly inhibit the motor neurons that
innervate antagonist muscles via
intervening reciprocal-sensory Iainhibitory interneurons (gray neurons)
256
what does reciprocal innervation (stretch reflex) result in?
in contraction of the stretched and
relaxation of the antagonist muscle
257
Is the stretch reflex a positive or negative feedback loop?
- negative loop used to maintain muscle length
258
How are muscles constantly balancing stretch levels?
1) The stretch reflex gain (the amount of force produced in response to a given stretch) is actively maintained.
-> If the gain is high, a small amount of stretch to the intrafusal fibers will
produce a large increase in the tension produced by the extrafusal fibers
2) The steady level of tension in muscles is mediated by Group II sensory
afferents also called muscle tone.
259
why is maintaining and modulating muscle tone necessary?
it is necessary to adapt to changing environments/demands.
e.g. standing on a moving bus, gain is dynamically modulated by
upper motor neuron pathways to compensate for changing
requirements as the bus stops and starts or drives smoothly to
maintain upright posture
e.g. doing stretching exercises, the gain must be reduced to support
lengthening of muscle fibers
260
how do gamma motor neurons regulate the gain of the stretch reflex?
by adjusting the level of tension in
the intrafusal muscle fibers.
261
what is movement the combined result of?
of sensory neurons, gamma motor neurons and alpha motor neurons.
262
what does activation of both alpha and gamma motor neurons prevent?
prevents decreased Ia firing during muscle shortening, allowing muscle spindles to operate at any muscle length.
263
what are some ways that muscles are constantly balancing stretch levels?
1) gamma motor neurons control levels of excitability in muscle spindles to
control the gain
2) gain also depends on excitability of alpha motor neurons
3) often alpha and gamma motor neurons are co-activated to regulate muscle spindles
4) both descending upper motor neuron projections and local circuits in the spinal cord can regulated the grain of the stretch reflex by exciting or inhibiting alpha or gamma neurons
5) inhibitory interneurons can also regulate Ia afferents via axo-axonal synapses
264
what is the function of golgi tendon organs?
they are important for reflex regulation of motor unit activity
265
where are golgi tendon organs located?
Located at the junction of a muscle and a tendon.
266
what are collagen fibres innervated by?
a single group of Ib sensory axons
267
what happens to collagen fibrils in the GTO when muscle contracts?
- When a muscle contracts, the force increases tension in the collagen fibrils in the GTO, compressing the sensory nerve endings.
268
What are GTOs most and least sensitive to?
- GTOs are most sensitive to muscle tension increase due to active muscle contraction.
- Insensitive to passive stretch
269
How do golgi tendon organs maintain a steady level of force, counteracting fatigue?
1) Ib sensory afferents synapse in the
spinal cord on inhibitory
interneurons that synapse with a
motor neurons, decreasing activity
of motor neurons to the same
muscle to exert negative feedback
regulation of muscle tension
2) Ib sensory afferents also synapse
on excitatory interneurons that
synapse with a motor neurons that
innervate the antagonistic muscles
to increase activity in the opposing
muscle
3) This arrangement protects the
muscle when exceptionally large
force is generated.
4) At lower levels of force, GTOs
maintain a steady tension level,
counteracting effects of fatigue
that would diminish muscle force
270
during passive muscle stretch, what does the muscle spindle do vs the golgi tendon organs?
During passive muscle stretch, muscle spindles signal rapidly, while GTOs signal slowly.
271
during active muscle contraction, what does the muscle spindle vs the golgi tendon organs do?
During active muscle contraction, the spindle is unloaded and its activity decreases, whereas the rate of Golgi tendon organ firing increases.
272
What is the difference in the function of the muscle spindle vs the golgi tendon organ?
1) Muscle spindles monitor & maintain
muscle length
2) Golgi tendon organs monitor &
maintain muscle force
273
What is the flexion reflex pathway?
1) Nociceptor afferents activate local
circuit neurons in the dorsal horn of
the spinal cord in a multi-synaptic
pathway (Purple: excitatory )
2) Stimulation of nociceptors in the foot
leads to withdrawal of the limb by
excitation of ipsilateral flexor muscles
and inhibition of ipsilateral extensor
muscles
3) The contralateral limb compensates
with the opposite reaction
274
what are rhythmic movements (walking, running, swimming) controlled by?
by local circuits in the spinal cord ‘central pattern generators’ (CPG)
275
what have animal models demonstrated to do with CPGs? (central pattern generators)
Animal models have demonstrated CPGs can control timing and coordination of complex patterns of movement and can also adjust complex movements in response to altered circumstances
276
Locomotion in a cat: Movement of a single limb during locomotion (walking, running) is a cycle consisting of two phases: what are they?
1) Stance: extending muscle, limb is in contact with the ground
2) Swing: muscle is flexed, and limb is off the ground
277
Locomotion in a cat: how is speed of movement increased?
Reducing stance
Swing remains largely constant
278
In quadrupeds, synchronic across limbs changes with speed, how?
1) Slow movement, left to right side
and back to front
2) As speed increases opposing limbs
synchronize (LH-RF)
3) At high speed, forelimbs are
synchronized as well as hindlimbs
279
locomotion in cat: when are cats in swing phase and when in stance phase?
1) swing phase: foot lifted
2) stance phase: foot on ground
280
Describe how the mammalian cycle of locomotion is organized by the central pattern generators in the spinal cord
1) Despite the complexity of locomotion,
co-ordinated movements do not require
descending projections from higher
centers
2) Even after transecting the spinal cord,
a (supported) cat can still walk on a
treadmill indicating that locomotion is
organized by central pattern generators
3) Local spinal cord circuits act as central pattern generators to control flexion & extension of limbs during locomotion
281
Ionic Basis of Mechanotransduction in Hair Cells
Hair cells, crucial components of the auditory system, play a pivotal role in mechanotransduction.
The basal and apical surfaces of hair cells are separated by tight junctions, creating distinct extracellular ionic environments.
1) Ionic Environments:
Stereocilia, located on the hair cell's apical surface, are immersed in endolymph (scala media), rich in K+ and poor in Na+.
A positive 80 mV potential is maintained by ion pumping in the stria vascularis.
2) Basal Environment:
The basal end of the hair cell is exposed to perilymph (scala tympani), characterized by low K+ and high Na+.
The potential in this region is 0 mV, similar to other body fluids.
3) Endocochlear Potential:
The disparity between endolymph and perilymph creates the endocochlear potential.
The hair cell's interior is 45mV more negative than perilymph and 125mV more negative than endolymph.
The intricate ionic balance at different hair cell surfaces is essential for mechanotransduction, highlighting the significance of endocochlear potential in auditory signal processing.
282
Ionic Mechanism of Hair Cell Mechanotransduction
- Mechanotransduction in hair cells involves an intricate ionic process crucial for auditory signal processing.
Ionic events:
1) Electrical Gradient and K+ Influx:
- The electrical gradient across stereocilia membranes drives K+ into the hair cells.
2) Depolarization and Channel Opening:
- K+ influx results in cell depolarization, triggering the opening of K+ and Ca2+ channels in the soma membrane.
3) Somatic K+ Channels and Repolarization:
- Somatic K+ channels open, facilitating K+ efflux towards the perilymph, contributing to repolarization.
Perilymph around the basal end is low in K+, reinforcing the outward movement of K+.
The sequential events, from the electrical gradient driving K+ into stereocilia to the repolarization through somatic K+ channels, demonstrate the intricate ionic basis of hair cell mechanotransduction. This process is essential for converting mechanical stimuli into electrical signals for auditory perception.
283
How do hair cells support extremely fast and energy-efficient repolarization?
The hair cell uses the different
external ionic environments of
its apical and basal surfaces
This arrangement ensures the
ionic gradient of the hair cell is
maintained even during
prolonged stimulation
284
Tuning and Timing in Auditory Nerve Processing
- Hair cells potential is biphasic
but they only release
neurotransmitter when
depolarized - auditory nerves fibers only fire in the rising
phase of the low-frequency
sounds (<3kHz)
- This results in ‘phase-locking’ which provides temporal
information that can be
compared between the inputs
from the two ears to localize
the source of a sound
285
What is labeled-line coding?
It is provided by the tonotopic organization of the basilar membrane
Topography is retained through the system, so information about frequency is also preserved.
286
The location of a hair-cell along the length of the basilar membrane corresponds to?
the frequency to which it is maximally
responsive.
287
how many hair cells does a single auditory fibre innervate?
Each auditory fiber innervates only a
single inner hair cell, thus transmits
information about only a small part of the frequency spectrum.
288
What does the tuning curve plot? (tuning and timing in the auditory nerve)
the minimum sound level
required to increase the
fiber's firing rate above
baseline
289
what is the characteristic frequency? (tuning and timing in the auditory nerve)
is the frequency at which a
nerve fiber will respond to
the weakest sound stimulus
290
Organization of the Ascending Auditory System: A Journey from Cochlea to Brainstem
The ascending auditory system, responsible for processing auditory stimuli, demonstrates a fascinating parallel organization from the cochlea to the brainstem.
1) Cochlear Nerve Terminals (CN VIII):
The journey begins with the Cochlear Nerve (CN VIII) whose terminals are housed in the spiral (cochlear) ganglion.
2) Auditory Nerve Branching:
Upon entering the brainstem, the auditory nerve undergoes branching to innervate the three distinct divisions of the cochlear nucleus, serving as the first synaptic relay.
3) Cochlear Nucleus Divisions:
The auditory nerve branches intricately connect with three primary divisions of the cochlear nucleus, each playing a crucial role:
Anteroventral division
Posteroventral division
Dorsal division
4) Tonotopic Organization:
Within these divisions, the tonotopic organization of the cochlea is preserved. This means that the spatial arrangement of neurons in these subdivisions reflects the frequency organization of the cochlea.
291
Cochlear nucleus
1) superior olivary complex (pons)
2) manuaral pathway
3) inferior colliculus (midbrain)
292
What is a key characteristic of auditory processing from the cochlea to the brainstem?
The journey of auditory processing from the cochlea to the brainstem is marked by a remarkable feature - a high degree of bilateral connectivity.
Bilateral connectivity
supports binaural
processing and localization
of sound based on binaural
differences
293
What are the two systems of the location of sound? what are some characteristics?
- two systems: ITD and IID
- Produced by the difference in time it takes for a sounds to reach each ear based on the location of the sound
source relative to each ear (Interaural time difference)
- Very small amounts of time (max 700 microseconds)
- Humans can detect ITDs of 10 microseconds
- Artificial manipulation of ITDs creates perception of sound arising from side of the leading ear
294
Interaural time differences (ITD)/location of sound
- are computed by binaural inputs to the medial superior olive (MSO) from the bilateral anteroventral cochlear
nuclei.
295
What does MSO contain
MSO contains cells with bipolar
dendrites extending both medially &
laterally
296
what do lateral dendrites receive (ITD)
receive ipsilateral
input
297
what do medial dendrites receive (ITD)
receive
contralateral input
298
what do MSO neurons function as?
MSO neurons function as
coincidence detectors, responding
maximally when both signals arrive
at the same time
Different neurons are maximally
sensitive to different ITDs
Axon projections from the
anteroventral cochlear nucleus
systematically vary in length to
create delays to compensate for
sounds arriving at slightly different
times at the two ears
The result is that cells are
responsive to sound sources in a
particular location (relative to ears)
299
do the systematic and
inverse variation in
delay lengths of the 2
inputs creates a map
of sound location?
Yes!
Neuron E: sounds on left
Neuron A: sounds on right
Neuron C: sounds at midpoint
300
What does ITD-based sound localization require?
phase-locking, which only occurs in
humans at <3kHz (recall, properties of
hair-cells)
An additional mechanism for sound
location is required for higher frequency sounds
301
At different frequencies, how does the human head act?
1) At frequencies >2kHz, the human
head acts as an acoustical obstacle
because the wavelengths are too
short to bend around it
2) When high-frequency sounds are directed at one side of the head, an
acoustical ‘shadow’ of lower
intensity is created at the far ear
3) The intensity difference provides a
cue about sound location
302
What is the function of lateral superior olive (LSO) and medial nucleus of the trapezoid body MNTB?
- they compute sound source position using IID
- LSO neurons receive direct
excitatory inputs from the
ipsilateral cochlear nucleus
- Contralateral inputs arrive
via inhibitory interneurons
in MNTB
- As a result, MSO
neurons fire most
strongly in response to
sounds arising directly
lateral to the listener,
ipsilateral to the LSO
- Excitation from
ipsilateral input will be
strong & inhibition from
contralateral input will
be weak
303
There are multiple mechanisms for the localization of sound. Explain the horizontal plane:
1) Interaural time difference
- Low frequency sounds
- MSO
2) Interaural intensity difference
- High frequency sounds
- LSO
304
There are multiple mechanisms for the localization of sound. Explain the vertical plane (elevation):
- Spectral filtering by the external pinna (outer ear)
- Processed in the dorsal cochlear nucleus
305
Monaural pathways
Monaural pathways from the cochlear
nucleus bypass the superior olive and
terminate in the nuclei of the lateral
lemniscus on the contralateral side of
the brainstem
- These pathways respond only to sound arriving from one ear
- Cells respond to different properties
e.g. (onset of sound, duration of sound)
306
Describe the integration of the ascending auditory pathways in the inferior colliculus
- Ascending auditory pathways from
LSO/MSO, lemniscal complexes &directly from the cochlear nucleus
all project to the auditory midbrain
‘inferior colliculus’ conveying: timing, intensity, frequency
- Brainstem inputs are computed into
a topographical representation
of auditory space
307
What sounds to neurons respond best to?
- Neurons respond best to sounds
originating in a specific region of
space
- Neurons also respond to complex
temporal patterns with preferences for
frequency or duration
308
the auditory thalamus
- All ascending auditory
information must pass through
the medial geniculate complex (MGC) of the thalamus
before reaching the cortex
- In some animals, the tonotopic inputs from brainstem converge
onto MGC neurons to generate
selective responses to
combinations of frequencies or
specific time intervals between
frequencies
309
the auditory cortex
- major target of ascending fibers from MGC
- essential for conscious perception of sound, including speech recognition
- contains topographic maps of the cochlea
- Because frequencies
are arranged
tonotopically along the
basilar membrane of
the cochlea, these
topographic maps can
be described as
tonotopic maps
- Integrates non-auditory information from other cortical and subcortical regions – activated by motor gestures (vocal and manual – specially in musicians!)
310
Ventral region of MGC
primary
auditory cortex
311
Dorsal region of MGC
belt and
parabelt regions / secondary auditory cortex
312
What are the two main subdivisions of the auditory cortex?
1) Primary auditory cortex
-> Receives point-to-point input from MGC & contains precise tonotopic map
2) Belt & parabelt:
-> areas of the auditory cortex receive more diffuse input from
the MGC and also from primary
auditory cortex, less precise tonotopic organization.
- these areas are strongly interconnected (reciprocal connections between belt and core)
313
What does the primary auditory cortex contain?
- contains irregular patches of neurons that are excited by input from both ears (EE) and patches of cells that are excited
by input from one ear and inhibited
by the other (EI)
314
How are EE and EI cells arranged?
- in alternating stripes, but the precise
function of this organization is
unknown
315
what areas are important in pitch perception?
Secondary regions of the the
auditory cortex may be important
in pitch perception which is
fundamental to music and vocal
communication as it allows us to
differentiate two overlapping
sounds
316
What areas are important for natural sounds?
- it is important for differentiating the temporal characteristics of auditory percepts
- this is important for natural sounds - highly ordered temporal structure - speech perception
- Electrophysiological recordings
demonstrate that some neurons are
responsive to the temporal order of
species-specific sounds and are
unresponsive to the same sound
played in reverse
317
What is the impact of humans having bilateral damage to the auditory cortex?
- have severe problems in processing the temporal order of sounds and with temporally complex acoustical signals e.g. music.
318
Wernicke's area
critical for language
comprehension is continuous with secondary auditory area
319
what type of activity is there in the auditory cortex before vocalization?
Activity in auditory cortex diminished just before a vocalization – filter for anticipated acoustical movements.
320
what is the evidence of lateralization in the auditory cortex?
-> Speech activates the
left auditory cortex
more strongly than the
right
->Music activates the
right auditory cortex
more strongly than the
left
->Inter-individual
differences in
lateralization
321
What is the function of the vestibular system?
1) Internal GPs for the body
2) Processes sensory information underlying motor responses and perception of: self-motion, head position, spatial orientation relative to gravity.
322
what is the vestibular system important for?
1) Balance
2) Gaze stabilization
3) Head movement and sense of orientation
323
what is the peirpheral vestibular system composed of?
the vestibular labyrinth, that is continuous with the cochlea
324
what cells does the vestibular system use?
- the same sensory cells 'hair cells' distributed in five sensory organ to measure linear acceleration and angular velocity
- cochlea: airborne sound stimuli
- labyrinth: effects of gravity from head movements
325
where are vestibular hair cells located?
- utricle
- saccule
- three ampullae
326
in the vestibular labyrinth, what are the 2 otolith organs? what do they respond to?
1) Utricle
2) Saccule
- they respond to linear accelerations of the head. static head position relative to the gravitational axis (head tilts)
327
in the vesitbular labyrinth, what do the 3 semi-circular canals respond to?
- rotational accelerations of the head
328
in the vestibular labyrinth, what are the specialized ionic environments created by? and what is the function of them?
- created by endolymph and perilymph
- tight junctions seal the apical surfaces of the hair cells such that endolymph bathes the hair cell bundle, separated from the perilymph that surrounds the basal portion of the hair cell
329
What are vestibular hair cells similar to?
auditory hair cells
330
why are vestibular hair cells and auditory hair cells similar?
- they both transduce minute displacements into receptor potentials
- Movement of the stereocilia toward
the kinocilium opens mechanically
gated transduction channels located at
the tips of the stereocilia to depolarize
the cell & induce neurotransmitter
release onto vestibular nerve fibers
(CN VIII)
- Movement of the stereocilia in the
direction away from the kinocilium
closes the channels , hyperpolarizing
the cell and reducing vestibular nerve
activity.
- Biphasic potentials
331
What is the arrangement of vestibular hair cells?
- hair cell bundles in each organ have specific orientation
- the the ampulla of each semi- circular canal, all hair cells are polarized in the same direction
- In the utricle &
saccule, the striola
divides the hair cells
into 2 populations
with opposite
polarities
- Between the
vestibular organs on
both sides of the
body, there is a
continuous
representation of all
directions of head
movement
332
What is the function of the otolith organs? what are they?
- utricle and saccule
- Detect displacements and
linear accelerations in
the head
- Otolith means ”ear stones”
- Named for the otoconia
which are embedded
crystals of calcium
carbonate in the macula
- The macula is a sensory epithelium in the utricle
& saccule
- Hair bundles project into a
gelatinous layer
- Above this is the otolithic
membrane, in which the
otoconia are embedded
333
what is the function of the otoconia?
- It makes the otholithic membrane heavier than the surrounding structures & fluids
334
what happens to the otolithic membrane when your head tilts?
- gravity causes the membrane to shift relative to the sensory epithelium
- the shearing motion between the otolithic membrane and the macula displaces the hair bundles, generating a receptor potential
-> a similar process occurs with linear accelerations
- the greater mass of the otolithic membrane causes it to lag behind the macula momentarily, inducing a transient displacement of the hair bundle
335
What is the difference between reflexes and voluntary movement?
Voluntary movement is organized around purposeful task, reflexes are not.
- in reflexes there tends to be one to one mapping with respect to stimulus and response. Which is not tru with voluntary movements, where multiple neurons of many brain regions coordinate muscles to move to a goal.
- effectiveness improves with purposeful practice.
- voluntary movements are generated internally and are not necessarily responses to environmental stimuli.
336
Described where the input for upper motor neurons come from and where it goes?
1) The basal ganglia is responsible for the initiation of intended movement and suppression of unwanted movement.
-> then travels to the descending systems (upper motor neurons)
-> goes to the motor cortex (planning, initiating, and directed voluntary movement)
2) Cerebellum: coordination of ongoing movement
-> goes to brainstem centers: rhythmic, stereotypes movements and postural control.
These signlas go to local circuit neurons and motor neuron pools in the spinal cord and brainstem circuits.
337
What is the somatotopic organization of the ventral horn in cervical enlargement?
- somatotopy of local circuit neurons in the intermediate zone (IZ)
-> medial IZ contains local circuit neurons that synapse with medial lower motor neurons while lateral intermediate zone nerons synapse with lateral ventral horn.
- the lateral white matter at the top (axons from the motor cortex -> skilled voluntary movements(
- the medial white matter (at the bottom) (axons from the brainstem - posture balance locomotion and orienting movements)
338
Describe the major pathways for descending motor control
1) 2 collections of upper neurons: cortex and brainstem
2) Brainstem -> medial (posture, balance)
3) Cortex -> lateral (voluntary, skilled movements)
339
Where do cortical motor areas receive input from?
basal ganglia, cerebellum, parietal lobe
340
Primary Motor Cortex
- Upper motoneurons mediate planning and initiation of movements.
- Receive input from basal ganglia and cerebellum by way of the thalamus.
- primary motor cortex is located in the precentral gyrus.
- low currents elicits movement and muscle contractions in this region.
- low threshold for eliciting movements is indicative of large and direct pathway from primary area to lower motorneurons of the brainstem and spinal cord.
341
What is the cytoarchitectonic appearance of the primary motor cortex in the human brain?
-> Upper motor neurons are pyramidal cells.
They are either betz cells or Non-betz pyramidal cells
342
What are the differences between Betz cells and Non-Betz Pyramidal cells in the primary motor cortex?
Betz cells:
* Largest cell soma in CNS
* 5% of projections to spinal cord
* important for distal muscle
control
* only found in primary motor
cortex
Non-Betz Pyramidal cells:
* Found in all divisions of motor
and premotor cortex
343
Corticospinal Tract
Pathway of Motor Cortical Neuronal Axons:
Internal capsule → Ventral surface of the midbrain → Cerebral peduncle → Pons → Ventral surface of the medulla → Spinal cord
Decussation in Medulla:
90% of fibers decussate in the caudal part of the medulla, forming the lateral corticospinal tract.
10% of fibers that do not cross form the ventral corticospinal tract, terminating bilaterally.
Termination and Function:
Lateral corticospinal tract terminates in the lateral ventral horn and intermediate zones.
Primarily controls distal limbs, forearm, and hand, influencing fine motor skills like writing, playing musical instruments, and buttoning clothes.
344
Corticobulbar Tract
Brainstem Projection of Corticobulbar Axons:
Corticobulbar axons give rise to bilateral collaterals in the brainstem.
Innervate multiple brainstem nuclei and mostly terminate on local circuit neurons.
Function of Corticobulbar Projection:
Controls muscles of the head, face, and neck.
Mediates various functions, including facial expressions, chewing, and tongue movements.
Details on Axon Termination:
Lateral corticospinal tract forms a direct pathway and terminates in lateral ventral horn and intermediate zones.
Some axons synapse directly onto α motor neurons to control distal limbs, forearm, and hand for fine motor control.
Ventral corticospinal tract arises from dorsal and medial regions of the motor cortex, serving axial and proximal muscles.
345
What is the functional organization of the motor cortex?
1) 1870’s Fritsch and Hitzig showed that electrical stimulation of the
motor cortex caused muscle contractions on the far side of the body.
2) Hughlings Jackson concluded that motor cortex had representation of
musculature. Epilepsy that induces partial seizures “marches”
systematically from one body part to another. Finger, hand, forearm,
arm, shoulder, and finally the face.
3) Wilder Penfield developed the "Montreal Procedure" which allowed
patients to remain awake and describe their reactions while the surgeon stimulated different areas of the brain.
-> He demonstrated that human motor cortex had map of musculature
Penfield correlated the location of muscle contractions with the site
of electrical stimulation of the surface of motor cortex.
-> He mapped the site of the precentral gyrus in more than 400
neurosurgical patients.
346
What did Intracortical Microstimulation show?
- Intracortical electrical stimulation in the 1960s showed the upper motor neurons in layer V of the motor cortex that project to lower motor neuron circuitry can be stimulated focally.
- When microstimulation was combined with recordings of muscle
electrical activity, small currents elicited excitation of several
muscles.
- Suggested that movements as opposed to muscles might be
organized.
- Movements could also be elicited by stimulation of sites that were
far from the original stimulation site. This suggests that local
circuits are involved in controlling movements.
347
Evarts 1960s Intracortical Recordings
Developed a pioneering system for recording from neurons in the motor cortex.
Observed that the firing rate of motor neurons increased in frequency proportionally to the applied force.
Noted an interesting phenomenon where firing rates increased before the actual development of force.
Proposed that the motor cortex plays a crucial role in the early phase of movement generation and planning.
348
1970s Spike Triggered Averaging
- Spike triggered averaging allows one to correlate the activity of an individual neuron in motor cortex with muscle acitvity
- animals perform a simple movement such as wrist flexion or wrist extension.
- It can be shown that a peripheral muscle group is
activated by one motoneuron.
- Observations confirmed that single upper motoneurons
contact several lower motoneuron pools.
----> Consistent with the idea that cortical neurons encode movements
instead of muscles
349
What did Michael Graziano discover?
- He used longer microstimulations in awake behaving monkeys to show fine-mapping of behaviourally relevant movements.
- Small currents elicited several muscle responses this showed that motor maps are of organized movements rather than individual muscles.
- Particular movements can be elicited by stimulation of widely separated motor cortex neurons -> action maps.
350
Purposeful Movements of the contralateral hand
- Prolonged (several seconds) microstimulation of the primary motor cortex induces purposeful movements in the contralateral hand.
- Coordinated movements resemble actions as if to feed, involving multiple joints of the contralateral hand.
351
What was discovered when performing directional tuning of an upper motor neuron in the primary motor cortex on a monkey?
- A monkey was trained to move a joystick in the direction indicated by a light.
- The activity of a single neuron
was recorded during arm
movements in each of 8 directions
- The activity of neuron increased before movements between 90 and 225° but decreased in anticipation of movements between 45 and 315°
- The directional tuning of the upper motor neuron in the primary motor cortex suggests specificity in neural activation, with increased firing rates before movements in certain directions and decreased activity in anticipation of movements in other directions.
352
When performing movement in a certain direction, when does neuronal firing increase?
Neuron's discharge rate was greatest before movements in a particular direction, which defines the neuron's preferred direction.
353
What is movement represented by?
- Movement is represented by the integrated activity of a population of bradly tuned upper motor neurons.
- The black lines indicate the
discharge rates of individual
upper motor neurons prior to
each direction of movement.
- By combining the responses of
all the neurons in the recording
session, a “population vector”
(red arrows) represents the
movement direction of the entire
population of recorded neurons
354
In the premotor cortex, how does it exert influence on motor behaviour? What are the differents between each way?
- The premotor cortex exerts both direct & indirect influences on motor behaviour
- Indirect effects are via reciprocal projections to the
primary motor cortex
- Direct effects are mediated by axons that project to the corticobulbar and corticospinal tracts
355
What are the divisions of the pre motor cortex?
1) Lateral & medial divisions serve different functional
specializations
356
what is the function of the lateral division of the premotor cortex?
2) Lateral premotor cortex especially important in ‘closedloop’ motor tasks e.g. a monkey trained to reach in
different directions depending on visual cue observed
3) Lateral premotor neurons fire at the appearance of the cue
& increase firing rates increase between cue and signal to
move
4) These neurons encode intention to move
5) Ventrolateral premotor cortex also contains neurons that
respond to observed movement performed by another
individual
357
what is a mirror motor neuron?
A mirror motor neuron is a neuron that fires both when an
animal acts and when the animal observes the same action
performed by another
358
In the experiment with monkeys discovering mirror motor neurons, what were some observations?
-> The same neuron does not
respond when the food is
placed with the aid of pliers, but it does fire during the
monkey’s reaching and
retrieval movements when
the monkey is allowed to
observe its reach
- The mirror neurons fire
when the behavior is
executed behind a barrier
(so the monkey can’t see
it’s own movement)
- These findings suggest
that the premotor cortex
plays a role in encoding
the observed actions of
others
359
What does the lateral premotor cortex require to function properly?
Lateral premotor cortex requires
external cues for selection of
movement. Lesions in monkeys,
impair “closed loop” tasks, the ability
to perform visual cue conditioned
tasks, even though they can see the
visual cue and they can perform the
motor response
- closed loop (cued)
360
What will patients with frontal lobe damage have issue doing?
Patients with frontal lobe damage
have difficulty initiating movements
in response to visual cues
361
what is the medial premotor cortex involved in?
- Medial premotor cortex also
mediates selection or initiation
of movements but is involved in
“open loop” conditions,
specifically internal cues
- open loop (spontaneous)
362
what happens if there is a lesion of the medial premotor cortex?
Lesions of the medial
premotor cortex in monkeys
reduces spontaneous
movements but preserves
ability to initiate movement in
response to visual cues
363
What do the brainstem motor centers work in concert with?
the motor cortex
364
where do pathways that influence lower motor neurons in the medial part of the ventral horn originate in?
Pathways that influence lower
motor neurons in the medial part
of the ventral horn originate in
upper motor neurons in the
vestibular complex, the reticular
formation and the superior
colliculus
365
what does Vestibular complex nuclei give rise to?
1) Give rise to medial vestibulospinal
tract
- Bilateral:
- Medial VS tract mediates feedback,
or responding to a disturbance of
body posture and stability signaled
by the semi-circular canals
- An example of feedback includes
extending your arms and the
dorsiflexion of your neck when you
trip
2) Give rise to lateral vestibulospinal tract
- Ipsilateral
- Lateral VS tract is involved
in proximal muscle
responses for stable
balance and upright posture
in response to signals from
the otolith organs
366
Where do reticular formation neurons project in? What is the function of them?
- Reticular formation neurons project in the reticulospinal tract to medial
ventral horn and modulate reflexes for
stereotyped movement
- These neurons receive input from
cortex, hypothalamus or brainstem and
initiate feedforward adjustments to
stabilize posture during ongoing
movements
367
How does the reicular formation mediate feedforward adjustements to stabilize posture during movement?
- In feedforward postural control,
cortical upper motor neurons
initiate both the primary
movement & a compensatory
movement to counter the
predicted destabilization of the
primary movement
- The reticular formation neurons
initiate the feedforward
adjustments
- The compensatory movement
precedes the primary movement
Example:
Ex. contraction of leg muscles to
maintain stability before you
attempt to pull on a handle with
your arm.
368
What are feedforward postural responses? What are feedback responses?
- Feedforward postural responses are
“preprogrammed” and typically precede the onset of
limb movement.
- feedback responses are initiated by sensory inputs that detect postural instability.
369
superior colliculus
- Additional brainstem structure of motor circuits
- Contains direct
pathway neurons to the spinal cord and indirect pathway through the reticular formation, that inputs to reticulospinal tract to control axial muscles in the neck, functions in head orientation
370
red nucleus
- Additional brainstem structure of motor circuits
- Projections are limited to cervical
level of the cord.
- Terminate in lateral regions of the
ventral horn and intermediate
zone.
- Controls arm / hand movements.
- Active prior to movement onset.
371
What takes place at the striola? What happens when there is a head tilt?
- orientation switches at the striola
- head tilt on the axis of the striola excites hair cells on one side and inhibits hair cells on the other
372
how do the hair cells orient in the saccules vs the utricles? What do they each respond to?
1) The hair bundles in the saccules are
oriented vertically – responds to translational movements on the
vertical plane and to
upward/downward head tilts.
2) The hair bundles in the utricles are
oriented horizontal – translational
movements in the horizontal
plane/sideway head tilts
373
What is the orientation of saccular and utricular maculae when looking at the entire head?
- Orientation of saccular &
utricular maculae are
mirrored on the two sides
of the head
- Tilting the head to one side
has opposite effects on
corresponding hair on the
other side.
374
How do otolith neurons sense tilt and acceleration?
- Vestibular afferents
innervating otolith organs
fire steadily when head
is upright
- Response to tilt is
sustained as long as the
tilting force remains -
increase or decrease in
firing depending on the
direction of the tilt.
- Hair bundle displacement will occur:
- tonically in response to head tilts
- transiently in response to translational hair movements.
375
Recap the Otolith organ
- Utricle codes motion in horizontal plane
- Saccule codes motion in vertical plane
- Together, they combine to respond to any linear force in
three dimensions
- Specific movements stimulate subsets of otolith hair cells,
while inhibiting other hair cells
- Changes in the polarity of hair cells in the otolith organs,
at the population level, comprehensively code head
position and movement
376
What are the functions of the semicircular canals? How many are there?
- 3 semi-circular canals sense head rotations
arising from self movement or angular
accelerations imparted by external force
(e.g. merry go round, roller coaster)
377
What is the anatomy of the semicircular canals?
- Sensory epithelium –crista- is found at a bulbous expansion (ampulla) on each canal.
- Hair bundles extend into a gelatinous mass – cupula
- The cupula bridges the entire width of the ampulla and prevents circulation of the endolymph
- All hair cells (hair bundles) point in the
same direction (no striola or mirror axis)
378
What is the function of the semicircular canal when there are rotational movements?
- Head turns on the plane of one of
the semicircular canals→
movement of endolymphatic
fluid→ distortion of the cupula
away from the direction of the
head movement→ displacement
of hair bundles within the crista→
receptor potential→
neurotransmitter release activates
vestibular nerve
379
What is the function of the semicircular canal when there are translational movements?
Produce equal forces on both
sides of the cupula – hair bundles
are not displaced
380
How are hair cells in the crista of each semicircular canal organized?
All hair cells in the crista of each semicircular canal are organized with their kinocilia in the
same direction. When the head moves on the plane of a semicircular canal, the entire
population of hair cells is depolarized.
- Opposite direction – hyperpolarized
- Orthogonal direction – Little or no response
381
How does the semicircular canal register each type of head movement?
Each type of head movement is registered by a corresponding semicircular canal in the same
plane of rotation.
- X axis - backflip
- Y axis – cartwheel
- Z Axis pirouette
382
What does the semicircular canal work in concert with? Describe this entire process.
- Each semicircular canal works in concert with the partner on the other side of the head (hair cells are aligned oppositely→ Opposite changes on
their firing rates. (Activity is increased in the pair member on the side toward which the head is moving)
- When head moves in horizontal plane e.g. to left, the cupula is pushed towards kinocilium on left, increasing firing but on right, the same movement pushes cupula away from kinocilium, decreasing firing.
- Push-pull arrangement operating for three pairs of canals. This provides a system that encodes
information about head rotation in any direction.
- Horizontal canals
- Superior/posterior
- Poster/superior
383
How can semicircular neurons sense angular accelerations?
- As with otolith afferents, the afferent nerves of the semicircular canals also maintain high baseline activity
- Information can be transmitted through both increases and decreases in firing
- Max increase in firing during acceleration
- constant velocity phase - firing rates return to baseline
- Maximum inhibition during deceleration - minimum firing rates.
- In constant velocity phase, the cupula can stay deflected up to 15 s, and it can undeflect while the head is still turning if there are prolonged acceleratory arcs (ships, airplanes, space vehicles, amusement park rides).
384
What does the vestibular system contribute to?
- It is multi-functional
1) Two major classes of reflex
- Those responsible for maintaining equilibrium & gaze during movement
- Those responsible for maintaining posture & balance
2) Higher order processes that are important for:
- sense of spatial orientation
- sense of self-motion
385
How is central vestibular processing multisensory? What does this provide?
1) Many neurons in the earliest stage of central processing, the
vestibular nuclei, also receive visual input
2) Many neurons in the vestibular nuclei function as premotor
neurons in addition to giving rise to ascending sensory
projections
- This provides a short-latency sensorimotor arc to drive rapid (~5ms) compensatory head & eye movements in response to
vestibular stimulation
386
How is central vestibular processing highly integrative?
The vestibular nuclei integrate input from:
- the canals & otoliths
- the contralateral vestibular nuclei
- cerebellum
- visual & somatic sensory systems
387
What are the 3 central vestibular pathways?
1) VOR (vestibulo oscular reflex)
2) Spinal Cord
3) Sense of self-motion
388
Key points about central vestibular pathways
- Vestibular nerves originate from cell bodies in the vestibular nerve ganglion, known as Scarpa's ganglion.
- The distal processes of these nerves innervate the semicircular canals and otolith organs, key components of the vestibular system.
- Central processes from the vestibular nerves project via the cranial nerve to reach the vestibular nuclei. Additionally, direct projections extend to the cerebellum.
389
what is the function of the vestibular-ocular relflex (VOR)
- The VOR is a mechanism for producing
eye movements that counter head
movements
- The VOR permits the gaze to remain
fixed on a particular point
- For example, when the head turns left,
activity in the left horizontal canal
excites neurons in the left vestibular
nucleus and this results in
compensatory eye movements to the right
390
Vestibular-Ocular Reflex: Simplified Pathway
1) Vestibular Nerve Fibers:
- From the left semicircular canal, vestibular nerve fibers project to the medial and lateral vestibular nuclei.
2) Excitatory Pathway - Lateral Gaze:
- Excitatory fibers from the medial vestibular nuclei cross to the contralateral abducens nucleus.
- This activates a motor pathway, contracting the lateral rectus muscle of the right eye.
- Simultaneously, an excitatory projection crosses midline to the left oculomotor nucleus, causing the medial rectus muscle of the left eye to contract.
3) Inhibitory Pathway - Maintaining Gaze Stability:
- Inhibitory neurons from the medial vestibular nucleus project to the left abducens nucleus.
- This decreases motor drive on the lateral rectus of the left eye, indirectly reducing the motor drive on the right medial rectus.
4) Outcome:
- The excitatory input from one side's horizontal canal results in eye movements towards the opposite side.
- This mechanism enables the maintenance of a fixed gaze despite head movement.
391
What are the net differences in left & right vestibular nerve firing induce 'nystagumus'
- When the head turns in a horizontal
plane, net differences in firing rates
of the left & right vestibular nerves
result in ‘physiological nystagmus’-
slow eye movements counter to the
direction of rotation & fast
movements in the same direction to
‘reset’ the eye position
- Damage to one nerve leads to
’spontaneous nystagmus’ i.e. eye
movements in the absence of head
rotation because of the net
difference in firing rates between the
two vestibular nerves
392
Describe Clinical Evaluation of the Vestibular System?
- Caloric testing of vestibular
function is used in diagnosis of
brainstem activity in unconscious
patients
- In conscious patients, injecting
cold water into one ear canal
induces slow movement toward
and fast movement away from the
irrigated ear (opposite for warm
water) because convection
currents in the canals mimic
rotational movement of the head
- In comatose patients
with intact brainstem
activity, only the slow
movement towards the
irrigated ear is observed
- Brainstem lesions
disrupt this movement
393
What happens if there is loss of VOR? (Vestibular-ocular reflex)
- Loss of the VOR due to vestibular damage has severe consequences
- Oscillopsia ‘bouncing vision’: inability to fixate visual targets while head is moving
- Unilateral damage can be compensated
- Bilateral damage leads to persistent sense that the world is moving
when the head moves because the oculomotor centers are not
receiving input from the vestibular systems so no compensatory eye
movements can be made
394
What are descending projections from the vestibular nuclei essential for? What are they mediated by?
- Essential for head and postural stability mediated by:
- vestibulo-cervical reflex (neck muscles)
- vestibulo-spinal reflex ( extensor muscles in trunk & limbs)
395
Vestibulocertical Reflex in the Central Vestibular Pathways
-Origination: Semicircular canals transmit signals to the Medial Vestibular Nucleus.
- Descent: Axons travel down the Medial Longitudinal Fasciculus.
- Termination: Reach upper cervical levels of the spinal cord.
- Function: Regulates head position through reflex activity in neck muscles triggered by semicircular canal stimulation.
- Example: Downward pitch (e.g., tripping) activates superior canals, prompting reflexive contraction of head muscles to pull up the head.
The Vestibulocervical Reflex, governed by the central vestibular pathways, ensures swift adjustments in head position by integrating signals from semicircular canals and coordinating reflexive responses in neck muscles.
396
Vestibulospinal Reflex in Central Vestibular Pathways
- Origin: Signals from Otolith organs are transmitted to the lateral vestibular nuclei.
- Pathway: Axons travel in the lateral vestibulospinal tract
- Termination: Axons reach the ipsilateral ventral horn of the spinal cord.
- Effect: Activation of extensor motor neurons and inhibition of flexor motor neurons.
- Net Result: Exerts a powerful excitatory influence on extensor (antigravity) muscles.
- Role: Mediates balance and contributes to maintaining an upright posture.
- Normally Suppressed: Typically under inhibitory control from the cerebral cortex.
- Lesions: Lesions can lead to decerebrate rigidity, indicating a loss of cortical suppression.
The Vestibulospinal Reflex, a crucial component of central vestibular pathways, ensures postural control and balance by influencing motor neurons in the spinal cord. Its regulation by the cerebral cortex highlights the complexity of maintaining upright posture and coordinated movement.
The Vestibulospinal Reflex, a crucial component of central vestibular pathways, ensures postural control and balance by influencing motor neurons in the spinal cord. Its regulation by the cerebral cortex highlights the complexity of maintaining upright posture and coordinated movement.
397
Descending Projections in Central vestibular Pathways
- Cutting the brainstem above the vestibular nuclei leads to 'decerebrate rigidity' characterized by rigid extension of the limbs.
- Intervention: Lesioning the vestibular nuclei alleviates decerebrate rigidity.
- This observation highlights the critical role of the vestibular system in maintaining muscle tone.
- The descending projections in central vestibular pathways play a crucial role in modulating muscle tone. Understanding the impact on muscle rigidity and the relief provided by lesioning the vestibular nuclei underscores the importance of these pathways in maintaining coordinated motor function.
398
Vestibular-Cerebellar Pathways: Cerebellar Integration and Adaptation
1) Descending Projections:
- Descending projections from the cerebellum target the vestibular nuclei.
- These pathways play a vital role in integrating and modulating vestibular signals.
2) Adaptive Changes:
- Cerebellar Importance: The cerebellum is crucial for adaptive changes in response to vestibular signals.
- Example: Adaptation of the vestibular ocular reflex involves altered firing of cerebellar Purkinje cells.
3) Purkinje Cell Functions:
- Integration of Signals: Purkinje cells integrate signals from otolith organs and semicircular canals, aiding in distinguishing head tilts from translational movements.
- Computation: Purkinje cells in various cerebellar regions perform computations essential for accurate signal interpretation.
4) Predictive Signals:
- Some cerebellar sub-regions generate predictive signals during self-generated movement.
- Purpose: These signals may cancel out vestibular or proprioceptive inputs, contributing to precise motor control.
5) Conclusion:
- The vestibular-cerebellar pathways showcase the cerebellum's significant role in integrating, modulating, and adapting to vestibular signals, highlighting its contribution to maintaining balance and coordinating movements.
399
Vestibular Pathways to Thalamus & Cortex
1) Thalamic Projection:
- Vestibular nuclei (lateral and superior) project to the ventral posterior nuclear complex of the thalamus.
2) Cortical Projection:
- Thalamic vestibular neurons extend projections to cortical areas near the central sulcus.
3) Cortical Areas:
- No "Primary Vestibular Cortex."
- Area 2v: Located posterior to the face representation in SI, associated with the dorsal visual stream.
- Area 3a: Divided into two regions.
- Parietoinsular Vestibular Cortex (PIVC): Critical for the sense of self-motion.
4) PIVC Functionality:
- Important for sense of self-motion.
Stimulation elicits vestibular sensations, and it's activated by vestibular stimulation.
5) Multisensory Nature:
Cortical neurons in these areas respond to proprioceptive, visual, and vestibular stimuli.
Reflecting the multisensory, integrative nature of central vestibular processing.
6) Conclusion:
Vestibular pathways extend to the thalamus and various cortical areas, including the PIVC, which plays a crucial role in processing the sense of self-motion. The involvement of multiple sensory inputs emphasizes the integrated nature of vestibular processing in the brain.
400
Does the vestibular system contribute to spatial orientation perception?
- In addition to contributing to reflexive control, the
vestibular system also contributes to our
perception of spatial orientation and self-motion
- Vestibular system function allows us to
- Detect the direction and magnitude of self-generated
motion
- Distinguish self-generated motion from the movement
of objects around us
- The vestibular system works in integration with the
visual system to achieve these functions
401
What are the basal ganglia?
- A group of nuclei that play a major role in normal voluntary movement.
- Do not have direct input or output connections to the spinal cord.
- Receive primary input from cortical structures and send their output back to prefrontal, premotor, and motor cortices.
- Motor functions are mediated by frontal areas of the frontal cortex.
402
What are the motor components of the basal ganglia?
1) Striatum
- Caudate
- Putamen
2 )Pallidum
- Globus pallidus
- Substantia nigra pars reticulata
3) Substantia nira pars compacta
4) Subthalamic nucleus
403
What are the inputs to the basal gnaglia nuclei?
1) Striatum (Caudate and Putamen)
- they are the input zone of the basal ganglia.
- The destination of the incoming axons from the cortex are onto dendrites of a class of cells called medium spiny neurons in the corpus striatum.
- Large dendritic trees of medium spiny neurons allow them to integrate information from a variety of cortical,
thalamic and brainstem structures.
- Axons from medium spiny neurons converge on neurons in substantia nigra pars reticulata and also globus pallidus.
- Globus pallidus and substantia nigra pars reticulata are the main output pathways of the basal ganglia.
404
Anatomical Inputs to Basal Ganglia
1) Cortical Inputs to Caudate:
- Primarily from multimodal association cortices and frontal lobe motor areas.
Control eye movement.
2) Cortical Inputs to Putamen:
- From primary and secondary somatosensory cortices, extrastriate visual cortices, premotor and motor cortices, and auditory association cortices.
3) Basal Ganglia Function:
Forms a subcortical loop connecting cerebral cortex to upper motor neurons in the 'corticostriatal pathway.'
Parallel corticostriatal pathways within the striatum reflect the functional organization of the cortex.
4) Topographic Mapping:
- Visual and somatosensory cortical projections are topographically mapped in different regions of the putamen.
Functional interconnected cortical areas overlap in the striatum.
5) Striatal Functional Units:
- Reflect specialization based on their cortical inputs.
405
Basal Ganglia Output Pathways and Inhibition
- Medium spiny neurons in caudate and putamen produce inhibitory GABAergic projections.
- Target nuclei: Internal globus pallidus and substantia nigra pars reticulata.
- Output functions of globus pallidus and substantia nigra pars reticulata are similar.
- Efferent neurons from internal globus pallidus and substantia nigra pars reticulata form major pathways to the motor cortex.
- Basal ganglia's main output is inhibitory due to GABAergic nature of efferent cells.
- Neurons in these output zones exhibit high spontaneous discharge.
- High discharge inhibits unwanted movements by affecting neurons in superior colliculus and thalamus.Basal Ganglia Output Pathways and Inhibition
406
Where do medium spiny neurons receive input from?
- Cortical neurons
- Local Circuit Neurons
- Dopaminergic neurons form the substantia nigra
- Other mSNs
- Raphe nuclei, brainstem
407
What is the function of medium spiny neurons?
- type of GABAergic projection neuron, principal neuron in the striatum, region of the brain within the basal ganglia.
- play role in basal ganglia circuitry and in motor control and coordination.
- Each MSN receives very few inputs from each
cortical axon
- Each cortical axon contacts many MSNs
- A single MSN integrates input from thousands
of cortical neurons
- Different inputs contact MSNs at different locations:
*1) Cortical: synapse on dendritic spines
* 2) Local circuit & thalamic neurons: synapse on dendritic shafts & close to soma
→ modulate effects of cortical inputs
- Dopaminergic inputs from substantia nigra pars compacta contact MSNs at the base of dendritic spines, close to cortical inputs
→ modulate effects of cortical inputs
- At rest, MSNs are hyperpolarized with
very little spontaneous activity
- Many excitatory inputs are needed to
excite MSNs
- MSNs activity may signal decision to move
408
is the basal ganglia output excitatory or inhibitory?
it is inhibitory, it plays a role in movement initiation by reducing inhibition.
409
Basal Ganglia in Eye Movement Control
-> there is evidence from eye movement studies that the substantia nigra pars reticulata is a crucial part of the basal ganglia output circuitry.
- axons are send to the deep layers of the superior colliculus.
- upper motoneuron in deep layers of superior colliculus command saccades.
- When eyes are not scanning the environment, these upper
motoneurons are tonically inhibited by spontaneously active
reticulata cells to prevent unwanted saccades.
- Just prior to a saccade, tonic discharge of reticulata neurons is
sharply reduced by input from the GABAergic medium spiny
neurons in the caudate, which have been activated by signals
from the cortex.
- Reduction in tonic discharge from reticulata neurons disinhibits
upper motoneurons of the superior colliculus, allowing them to
generate the burst of action potentials that command the
saccad
410
disinhibitory circuit. what is it? what is an example of one?
- eural circuit arrangement where a chain of nerve cells (neurons) is organized to suppress or reduce inhibition, leading to the activation or excitation of a downstream neuron or group of neurons.
- an example of one is the description of eye movement control involvin the susbstantia nigra pars reiculata.
411
What are the two circuits within the basal ganglia? What is the description of each?
1) Direct Pathway
- serves to release upper motorneurons from tonic inhibition. Facilitates movement.
2) Indirect pathway.
- Serves to increase the tonic level of inhibition. Inhibits movement.
412
Describe the direct pathway in the basal ganglia. And also the indirect. Compare them.
- Activation of the
direct pathway
inhibits the globus
pallidus, internal
segment, to release
inhibition on the
VA/VL thalamus to
activate cortex
- Cortical activation of the
striatal indirect pathway
(yellow), inhibits the
external segment of the
globus pallidus, to
release the inhibition on
the subthalamic nucleus,
to activate the globus
pallidus internal segment,
to inhibit the VA/VL
thalamus, inhibiting
output to cortex.
- Direct and indirect
pathway function in
opposition.
- The balance of
activity between the
direct and indirect
pathways determines
if the BG will facilitate
or suppress
movement
413
Describe the dopaminergic modulation of direct & indirect pathway in the basal ganglia.
- Dopamine acting at D1
receptors enhances
activity of the direct
pathway
- Dopamine acting at D2
receptors suppresses
activity of the indirect
pathway
- Because the indirect
pathway opposes the
direct pathway, the net
effect of dopamine is to
decrease the inhibitory
outflow from the BG
414
Basal Ganglia in Motor Control and Goal-Directed Behavior
- Basal ganglia circuits not only facilitate movement but also suppress competing motor programs to support goal-directed behavior.
- The 'Focused Selection' concept proposes that the direct and indirect pathways are organized in a center-surround manner.
- Direct Pathway: Mediates focused activation of a functional unit.
- Indirect Pathway: May suppress the activity of surrounding functional units.
- Both pathways need to be co-activated for the smooth execution of motor behavior.
415
What insight to neuropathologies provide into the functions of the basal ganglia?
- substantia nigra degenrates
- caudate and putamen shrink
416
How do the indirect pathway of the basal ganglia relate to Huntington's disease?
- Huntington’s disease: neurons from the caudate degenerate.
- In the absence of normal inhibitory input, the external globus pallidus cells become more active.
- This activity reduces the excitatory output of STN to the internal segment of the globus pallidus.
- Inhibitory output of the globus pallidus is therefore reduced.
- Upper motoneurons can now be activated by inappropriate signals.
- Leads to ballistic, choreic movements of Huntington’s disease.
417
What are the characteristics of the indirect pathway in the basal ganglia?
- The indirect pathway can be considered a mechanism to
“brake” or “focus” the normal activation of the direct pathway.
- Consequences of imbalances in this fine control mechanism
are apparent in diseases that affect the subthalamic nucleus (STN) - small nucleus in basal ganglia.
- Disorders of STN remove a source of excitatory input into the
internal globus pallidus and reticulata, and thus abnormally
reduce the inhibitory outflow of the basal ganglia.
- A basal ganglia syndrome called hemiballismus, characterized
by violent, involuntary movements of the limbs, is the result of
damage to the STN.
- The involuntary movements are initiated by abnormal
discharges of upper motoneurons that are receiving less tonic
inhibition from the basal ganglia.
418
Does a GABA agonist produce involuntary movements resembling hyperkinesia?
Yes
419
GABA agonist - muscimol effect
- decreases the tonic
inhibition of superior colliculus.
This causes monkeys to generate spontaneous,
irrepressible saccades that resemble the involuntary
movements characteristic of basal ganglia diseases
such as hemiballismus and Huntington’s disease.
420
What is Parkinson's Disease?
Major degeneration of the nervous system.
421
What are the three cardinal signs of Parkinson's disease and what are several other motor problems also present?
Three cardinal signs:
1) tremor at rest -3-6 Hz
2) Rigidity
3) Bradykinesia
Several other motor problems:
- Abnormal postural reflexes
- Minimal facial expression (masked face)
- Walking entails short steps (festination)
- Stooped posture
- Paucity of associated movements (limited arm movements in gait)
- Micrographia
- Saccades diminished in frequency and amplitude.
- Speech - hypophonia
422
What is parkinson's disease associated with?
- dementia
- dyskinesias
- Progressive loss of dopamine in neurons of substantia
pars compacta. Cause of degeneration not known.
- Since the disease is localized to neuronal degeneration
in a restricted area, and since the projections from this
area are local, this has provided a rich opportunity for
therapeutic intervention.
423
How is Parkinson's a hypokinetic movement disorder?
- In the healthy brain,
dopamine acts at D1 &
D2 receptors to decrease
inhibitory outflow of the
BG, allowing excitation of
upper motor neurons
- In Parkinson’s brain,
dopamine from the SNPC
is reduced, making it
more difficult to initiate
and terminate movement
424
what is the most effective treatment for parkinson's?
Most effective treatment
is combined
pharmacology & DBS
- Levodopa
425
What are non-motor functions of the basal ganglia?
- Both Parkinson’s & HD are
associated with cognitive
& emotional dysregulation,
hinting at other major
roles of the basal ganglia
-Basal ganglia also plays
key role in cognitive &
affective behaviors
- Parallel loops originate in
different regions of
cerebral cortex
426
what are the two loops in the basal ganglia that are responsible for non-motor functions? describe the role of each.
1) Dorsolateral prefrontal
loop:
- May regulate initiation &
termination of cognitive
processes
2) Limbic loop
- May regulate emotional &
motivated behaviour &
transitions between mood
states
-The ventral striatum is
particularly implicated in
reward, motivation and
emotion
427
What is the function of the cerebellum?
- Does not project directly to the motoneurons of the
spinal cord.
- Modifies movement by regulating upper motoneurons in
regions such as the motor cortex
- Made up of a cerebellar cortex and deep cerebellar
nuclei.
- The primary function is to detect ‘motor error’ i.e. the
difference between intended & actual movement , error
correction in real time and in motor learning and
sensory-motor integration.
428
what is the organization of the cerebellum?
- 3 main parts defined by source of input:
1) Cerebrocerebellum
2) Spinocerebellum
3) Vestibulocerebellum
429
What are the characteristics of the cerebrocerebellum?
* Receives indirect input from
many areas of cerebral cortex
* Particularly well developed in
humans and other primates
* Regulates highly skilled
movement, especially planning
& execution of complex spatial
& temporal sequences of
movement (e.g. speech)
430
What are the characteristics of the spinocerebellum?
* Receives direct input from
spinal cord
* Lateral part regulates
movement of distal
muscles
* Central part (‘vermis’)
regulates movement of
proximal muscles & some
eye movements
431
What are the characteristics of the vesitbulocerebellum?
- Oldest part of the cerebellum
* Caudal-inferior lobes of
cerebellum
* Flocculus & nodulus
* Receives input from vestibular
nuclei in brainstem
* Primarily involved in movements
to maintain posture & balance &
the vestibulo-ocular reflex
432
432
How does the cerebellum communicate with other parts of the nervous system?
- via the 3 cerebellar peduncles
1) Superior cerebellar peduncle
2) Middle cerebellar peduncle
3) Inferior cerebellar peduncle
433
What are the characteristics of the Superior cerebellar peduncle?
- Almost an entirely efferent
pathway
- Neurons located in deep
cerebellar nuclei project to
--> Upper motor neurons in primary
motor and premotor cortices
--> Upper motor neurons in the
superior colliculus to control
orienting movements
434
What are the characteristics of the Middle cerebellar peduncle?
- Afferent pathway to the
cerebellum
- Cell bodies located in the
contralateral pontine nuclei
- Largest pathway in the
brain containing more than
20 million axons
435
What are the characteristics of the Inferior cerebellar peduncle?
- Contains multiple afferent
& efferent pathways
- Afferents from vestibular
nuclei, spinal cord,
brainstem tegmentum
- Efferents to vestibular
nuclei & reticular formation
436
What provides the largest input to the cerebellum?
- Cerebral cortex
- Indirect projection via the ipsilateral pontine nuclei
- Pontine axons ‘transverse
pontine fibres’ cross the midline
to entre the contralateral
cerebrocerebellum via the middle
cerebellar peduncle
437
What are different types of projections to the cerebellum? What do they all have in common?
Projections to the cerebellum:
* Motor and premotor cortex
--> Motor control
* Somatic sensory cortex
--> Sensory-motor integration
* Visual motion regions of the
posterior parietal cortex
(magnocellular processing
stream)
---> Visuomotor coordination
ALL of these regions project to the pontine nuclei.
438
How is sensory information carried to the cerebellum?
Sensory information carried
by the vestibular axons in
the 8th cranial nerve &
axons from the vestibular
nuclei in pons & medulla
projects to vestibulocerebellum via the
inferior cerebellar peduncle.
439
How do somatosensory neurons project in the cerebellum?
- Somatosensory neurons in the
dorsal nucleus of Clarke in the
spinal cord & the external
cuneate nucleus of the caudal
medulla project to the
spinocerebellum via the inferior
peduncle
- Proprioceptive information from
the face travels via the
mesencephalic trigeminal
nucleus to the spinocerebellum
440
How is somatosensory input to the cerebellum organized?
- Somatosensory input to the
cerebellum is organised in
topographic maps in the
spinocerebellum
- These maps are ‘fractured’
in that each body area is
represented multiple times
by spatially separated
groups of cells
- Brainstem & spinal inputs
remain ipsilateral so
representations are of the
ipsilateral side of the body
441
What is the function of the inferior olive in the cerebellum?
- The inferior olive
sends modulatory
inputs to the
contralateral
cerebellum via the
inferior peduncle
- These inputs are
important in
cerebellar learning
and memory
442
Projections from the cerebellum
- Most of the cerebellar cortex projects to deep cerebellar nuclei prior to reaching the target.
- Thalamus is a major relay target from the cerebellum to
motor cortex.
- There are 4 major deep nuclei: Dentate (largest), Interpositus (2), Fastigial.
- Dendate nucleus: Associated with the cerebrocerebellum. Premotor cortex (motor planning)
- Interposed and Fastigial nuclei: Associated with the spinocerebellum. (motor cortex and brainstem (motor execution)
- interposed nuclei mediate limbs
- fastigial nuclei mediate axial and proximal muscles
- fastigial nuclei are more medial than interposed nuclei
- Vestibular Nuclei:
- Considered part of deep cerebellar nuclei.
- Play a role in the vestibulocerebellum
- lower motor neurons in spinal cord and brainstem (balance and vestibulocular regulation).
443
What happens if there is damage to the cerebellum?
- Causes persistent errors in movement.
- Errors in movement are on the same side of the body as the cerebellar deficit.
- Somatotopic organization allows for some muscle
groups to be affected but others are not affected.
- Alcohol abuse can cause damage to the cerebellum
– particularly in the anterior portion.
444
Ataxia
difficulty producing smooth, wellcoordinated movement.
445
What happens if there is damage to cerebrocerebellum?
deficits in coordination and visuomotor
integration.
446
what happens if there is damage in vestibulocerebellum?
impairs ability to stand upright and
maintain a direction of gaze.
447
what happens if there is damage in the spinocerebellum?
difficulty walking.
448
what are signs of damage to the cerebellum?
- Dysmetria: over or under reaching a target
- Action or intention tremors
- Speech deficits
- intention temors
- tandem walking
449
Describe Cellular Circuit organization of the Two Inputs to the Cerebellum.
1) Mossy Fibers
- Arise from many areas in the cortex &
brainstem
- Synapse onto granule cells (highly abundant).
- Give rise to parallel fibers which have excitatory synapses onto the dendritic spines of the Purkinje cells.
2) Climbing fibers
- Arise from inferior olive.
- Contact Purkinje cells directly.
- Excitatory synapses onto Purkinje cells.
450
What are some characteristics of Purkinje Cells?
- They project to the deep cerebellar
nuclei.
- These are the only output cells of the cerebellar cortex.
- GABAergic inhibitory output from Purkinje cells.
- This inhibition modulates the excitation from
mossy fibers and climbing fibers that branch to the deep cerebellar nuclei.
451
What is the Extramission theory of vision?
How does the visual system work?
1) Plato- 4th century BCE
-> believed that the eye sent out rays, which seized objects
2) Theophrastus - 3rd century BCE
- the eye has an internal fire from which these rays emanate
3) Galen - 2nd centry CE
- thought optical pneuma was emitted from the eye
- considered the lens to be the origin of vision, as it was known that cataracts obstructed vision.
4) 2002 - Winer et al
- found that 50% of american adults believe in extramission theory
452
What is the Intramission theory of vison?
How do we see?
1) al-razi 10th century CE
- noted that light levels controlled pupil dilation and contraction
2) lbn al-haythman 10th-11th century CE
- described how bright light disturbed the eye
3) lbn Sina - 10th-11th century CE
- argues in favour of the intromission theory
453
the cornea
- clear tissue at the front of the eye, It deflects incoming light
454
the pupil
- it is the opening in the iris, and opening and closing it controls the amount of light entering the eye
455
the lens
- the lens focuses incoming light on the retina, and the ciliary muscles change its shape to change its refractive power
456
the retina
- it is the light sensing neural tissue at the back of the eye
457
why do the pupils look black?
- this is because the cornea, lens, liquid humors and retina are clea, and behind the retina lies the retinal pigment epithelium which is dark in colour.
458
the fovea
- it is the part of the retina responsible for high resolution vision
459
the optic nerve
- it is build from retinal ganglion cell axons and is the pathway whereby retinal signals get sent to the rest of the brain
460
what is the effect of reducing and increasing pupil size?
1) Reducing pupil size reduces optical abberations of light passing through the lens and increases the depth of field (the distance within which objects are seen without blurring)
2) increasing the pupil size increases the amount of light entering the eye to allow for vision of dim environments
461
what is the primary responsibility of the cornea and lens?
- focusing images on the retina
- the cornea (due to differences in refractive power between it and air) provides around 2/3 of the eye's optical power
- when swimming, water eliminates the cornea's refractive power
- the thickness of lens is adjusted by the cilary muscle, allowing the focal plane to be "tuned"
- when viewing distance objects, the lens is thin
- when viewing close objects, the lens is less thick, providing increased refractive power
462
What happens when the accommodation of the lens can't focus an image on the retina?
- corrective lenses are required
463
What is myopia?
- In myopia (nearsightedness), images are focused in front of the retina (far away images are blurry)
- it affects around 50% of people
464
What is hyperopia?
- In hyperopia (farsightedness), images are focuses (virtually) behind the retina (close objects blurry).
465
What is accommodation as power decreases with age?
- as we age, the lens loses elasticity
- when we look at far away objects, we relax our eyes muscles and lens, and contract them when looking at nearby objects
- as such, as we age, near objects can't be focused on the retina as well
- this is called presbyopia, and can require reading glasses to compensate
466
What is Astigmatism?
- Arises from spherical abberations of the eye
- these result in different focal points for different parts of the visual field
- can usually be corrected for with glasses of contact lenses
467
Describe the anatomy of the retina
- the macula is the area of the retina responsible for central, high resolution vision.
- the fovea is the central part of the macula, responsible for our highest resolution vision
- the optic disk, comprises of nerve fibres leaving the eye, produces a blind spot in the visual field
468
Describe the blind spot produces by the optic disk in the retina
- there are no photoreceptors in the optic disk, results in a blind spot
- the mechanism is not completely understood, but the visual system 'fills in' the scotoma
469
Describe main characteristics about the Fovea
- the fovea exclusively contains densely packed cone photoreceptors (around 200 fold increase in cone density)
- Visual acuity is increased in the fovea because 1) foveal cones are skinner and more densely packed than outside the fovea, 2) the rest of the retinal cell are pushed away to the side, and 3) it is avascular
- outside the fovea, rods vastly outnumber cones
470
how many rods and cones does the human retina have?
- the human retina has around 90 million rods and only 4.5 million cones
471
Describe the anatomy of the retina
- rods and cone photoreceptor convert incoming light into a neural signal
- the retina is a complex, layered neural tissue that parses incoming light into different visual channels (such as color, movement, edges, etc)
- incoming light passes through the entire retina before being detaches by the light-sensing photoreceptor outer segments
- the retina is comprised of 5 main neuronal cell types
472
what are the 5 main neuronal cell types that comprise the retina?
- photoreptors
- horizontal cells
- bipolar cells
- amacrine cells
- ganglion cells
473
What it the lifespan of photoreceptor outer segments?
- light-sensing outer segment disks have a lifespan of around 12 days
- new disks are made at the base, and ones at the tip are shed
-shed disks are phagocytosed by the retinal pigment epithelium
474
Where does the visual signal start?
- in photoreceptors
- photoreceptors signal via graded membrane potentials (i.e. they don't fire action potentials)
- photoreceptors release glutamate in the dark
475
What is the role of cones and rods for colour vision?
- Rods function under dark (scotopic =) conditions and do not confer colour vision
- Cones function under light (photopic) conditions and confer colour vision and high resolution central vision
476
What is the mode of action of photoreceptors when light is present?
- photoreceptor hypolarize in the presence of light
- they signal via graded potentials
-> graded potentials signal intensity via amplitude and length of response
-it is thought that action potentials are needed to pass information over long distances, whereas distanced in the retina are short, so graded potentials are sufficient
- photoreceptors release less glutamate when light is turned on
477
How does Cyclic-GMP gates channels regulate photoreceptor membrane potential?
- In the dark, Na+ and Ca2+ ions flow into the outer segments, and K+ ions flow out of the inner segment
- influx of Na+ and Ca2+ through cGMP gated channels in the dark keeps photoreceptors relatively depolarized
- in the presense of light, cGMP levels in the outer segment decrease and the channels allowing influx of Na+ and Ca2+ close, resulting in membrane hyperpolarization.
478
Describe the phototransduction cascade
- The photopigment contains a molecule of retinal (vitamin a derivative) attached to an opsin
- the specific photoproperties of the photopigment/opsin confer the wavelength specificity differences between different types of photoreceptors
- retinal, upon absorbing a photon light, converts fro an 11-cis to an all-trans configuration
- conversion to all-trans retinal activates transducin, which actives phosphodiesterase (PDE), which in turn hydrolyzes cGMP
- lower [cGMP] results in the closure of cGMP-gates ion channels, leading to membrane hyperpolarization
- amplification along the intracellular cascade means that even the response to a signal photon of light can be significant
- activation of a single rhodopsin molecule (the opsin in rods) can activate around 800 molecules of transducin
- each transducin activates a single phosphodiesterase, but each PDE can hydrolyze around 6 cGMP molecules
- a single photon can close around 200 cGMP gated channels (around 2% of the channels open in the dark) and cause a 1 mV hyperpolarization
479
How is the phototransduction cascade stopped?
- Activated rhodopsin is phosphorylated by rhodopsin kinase, which allows arresting to bind to rhodopsin and stops rhodopsin from activating transducin - arresting the phototransduction cascade
480
Describe the steps of the retinoid cycle
1) All-trans retinal dissociated from the opsin and diffuses into the cytosol in the outer segment
2) All trans-retinal is converted to all trans retinol
3) All-trans retinol is shuttled from the outer segment to the retinal pigment epithelium via interphotoreceptor retinoid binding protein (IRBP)
4) All-trans retinol is converted to 11-cis reitnal
5) 11-cis retinal is shuttled back to the photoreceptor outer segment, by IRBP, where it combines with the opsin (resulting in new active photopigment molecules)
481
What is the difference between cones and rods when it comes to light?
1) Cones are active in bright conditions, and because they make up the fovea, they convey high resolution visoon. Since there are multiple cone opsins, they confer colour vision.
2) Rods are more sensitive to light and thus signal in dim environments, but because they are relatively spread out and express a single opsin, they only confer low resolution in monochromatic vision.
482
What are the 3 different cone types? What are the characteristics of each?
- they have different spectral sensitivities
- short wavelength, S cones prefer blue light. S cones make up around 10% of cones and are uncommon in the foveal center.
- Medium wavelength, M cones prefer green light. The M and L cone ratio appears to differ between people (from 1:1 to 4:1) without significant impact on colour vision.
- Long wavelength, L cones prefer red light
- Simply having specific wavelength sensitive photoreceptors does not produce color vision, color vision is a result of comparing and contrasting responses generated by different cone types.
483
What are colour blind individuals missing?
- they are missing a cone type
- approximately 8% of the male population is colour blind (the genes coding red and green opsins are on the X chromosome)
- both protanopes and deuteranopes have trouble distinguishing red and green, and are generally referred to as red-green colour blind.
484
What is achromatopsia?
- complete colorblindess
- can arise from a total lack of functioning cones (it can also arise from damage to the color vision part of the brain)
- the prevalence is roughly 1 in 30,000 people
- on the island of Pingelap in South Pacific, around 10% of the population are achromatopes
- in 1775, a typhoon killed most of the islands inhibitants, and the population was largely repopulated by the king, who himself is an achromatope
485
How do photoreceptors signal to bipolar cells?
- via glutamate
- photoreceptors, upon absorbing photons, hyperpolarize and decrease their release of the neurotransmitter glutamate from synapses in their axon terminals.
- Glutamate released from photoreceptors binds to glutamate receptors on bipolar cell dendrites
- Bipolar cells, when excited (depolarize), release glutamate from synapses in their axon terminals
- the glutamate released from bipolar cells bind to glutamate receptors on ganglion cell dendrites, exciting (depolarizing) ganglion cells and causing them to fire action potentials which propagate out of the retina via the optic nerve.
486
What are the characteristics of ON bipolar cells? How are they generated?
- they are generated by distinct glutamate receptors
- ON bipolar cells have metabotropic glutamate receptors on their dendrites
- this metabotropic receptor is linked via an intracellular pathway to a Na+ channel
- The Na+ channel is closed when glutamate is bound, so ON bipolar cells are hyperpolarized in the dark and only active (depolarized) in the light
487
What are the characteristics of OFF bipolar cells? How are they generated?
- they are generated by distinct glutamate receptors
- OFF bipolar cells have ionotropic (the receptor and the ion channel are one and the same) glutamate receptors on their dendrites.
- in the dark, when photoreceptors release glutamate, OFF bipolar cells are active (depolarized).
488
Where do ON and OFF bipolar cells send their axons?
- to different layers in the retina
-bipolar cell bodies reside in the inner nuclear layer
- Bipolar cell axon terminals reside in the inner plexiform layer
- OFF bipolar cells stratify in the upper layers of the IPL and connect to OFF ganglion cels.
- ON bipolar cells stratify in the deeper layers of the IPL and connect to ON ganglion cells.
489
Where do bipolar cells pass photoreceptor signals onto?
- ganglion cells!!
- Glutamate released from bipolar cells
binds to glutamate receptors on ganglion cell dendrites, exciting (depolarizing) ganglion cells and causing them to fire action potentials which propagate out of the retina via the optic nerve.
490
What is the 'vertical' retinal pathway?
photorecpetor -> bipolar cell -> ganglion cell
491
When photoreceptor signal enters the retinal ganglion cell, what happens?
- the intensity of light is transformed into the frequency of action -potentials in retinal ganglion cells.
492
Describe the process of light adaptation in the retina
- Ganglion cell firing rate is not an absolute measure of light intensity
- ganglion cell firing rate is related to the difference between stimulus and background intensity
- at a given background level, a spot's evoked response rate is proportional to its intensity over approximately 2 log units of light intensity
- this adaptation allows us to see changes in light intensity across several log units of different background intensities (as you encounter everyday life)
493
In the fovea, what do the cones form?
They form the center of an on-centered and an off-centered pathway.
494
Why are the receptive fields larger outside the fovea?
- because more photoreceptors feed into a single ganglion cell, so the receptive fields are larger.
495
Describe image forming vision in the daytime
- cone bipolar cells synapse directly with ganglion cells
496
Describe image forming vision in the nighttime
- rods have their own specific bipolar cell (it is an ON bipolar cell)
- rod bipolar cells do not generally make direct synapses with ganglion cells
- rod bipolar cells make glutamatergic synapses with All ("A2") amacrine cells.
- all amacrine cells in turn form electrical synapses (with gap junctions) with ON cone bipolar cells.
- therefore rod signals piggy-back onto the cone bipolar system to reach ganglion cells.
497
Does the retina extract multiple visual features?
Yes! Different ganglion cells extract unique visual features, such as edges, motion, colour, etc.
498
What tiles the retina?
- repeating circuit modules tile the retina
- each type of ganglion cells represent different pixel-sensory types
- within a given pixel area (within a given part of the visual field), each type of pixel sensory (each types of ganglion cell) is present.
- since each ganglion cell type receives inputs from a specific microcircuit of specific bipolar and macrine cells, these circuits also repeat across the retina.
499
What did functional phenotyping of retinal ganglion cells reveal?
- different retinal ganglion cells like to see different things
- over 40 distinct functional cell types in the mouse retina
- A similar functional profiling has not yet been done in human retina, but it seems there are fewer (~15) ganglion cell types in human retina, and ~80% are made up by 4 cell types (ON and OFF midget and ON and OFF parasol)
500
What is a receptive field for a visual neuron?
it is a area in space in which light stimulation drives a neuronal response
501
what are ON-center ganglion cells excited and inhibited by?
They are excited by light in their receptive field center and inhibited by light in their receptive field surround.
502
what are OFF-center ganglion cells excited and inhibited by?
They are inhibited by light in their receptive field center and excited by light in their receptive field surround.
503
Where do ON and OFF ganglion cells project to?
They project their dendritic arbors to different layers of the IPL, where they receive input from ON and OFF bipolar cells.
504
What are ganglion cells not good and good at responding to?
- ganglion cells are not good at responding to diffuse illumination, but are good at responding to luminance contrast within their receptive field.
505
How do surround receptive field arise?
- through lateral inhibition
- horizontal cells provide negative feedback to photoreceptors
- Amacrine cells can provide lateral inhibition to bipolar cells and ganglion cells
506
How do horizontal cells provide surround inhibition to photoreceptors?
- Horizontal cells provide negative feedback to photoreceptors, resulting in surround inhibition
- When photoreceptors hyperpolarize in the presence of light, they release less glutamate
- This decrease in glutamate results in less activated glutamate receptors on horizontal cell dendrites, which causes horizontal cells to also hyperpolarize
- Horizontal cell hyperpolarization negatively feeds back to photoreceptors and causes photoreceptors to slightly depolarize
- Horizontal cell feedback can get passed down to retinal ganglion cells
507
What are the ganglion cell receptive field properties?
- The same visual stimuli can drive remarkably different responses depending on which part of a ganglion cell receptive field it falls up
- each ganglion cell has a preferred size visual input (usually a spot that perfectly matches its receptive field center)
508
What is the difference between Luminance vs brightness?
- Luminance is the physical measurement of light intensity
- Brightness is the sensation of elicited by light intensity
- the same luminance can have remarkably difference brightness, depending on the context
- some of this difference could arise from lateral (surround) effects in the retina
509
Some ganglion cells are sensitive to the direction of motion of a moving image, and some selective retinal ganglion cells have different prefered directions. What generates direction selective responses?
- Asymmetric lateral inhibition
- Direction selective ganglion cells receive inhibitory input from starburst amacrine cells.
- Starbust amacrine cells are only connected to one side of the direction selective ganglion cell's dendritic/receptive field.
- When light stimuli move in the prefered direction, the ganglion cell is excited before the stimuli reaches the starburst amacrine cell.
- when light stimuli move in the null direction, starbust cells are activated before the ganglion cell receives excitatory input from bipolar cells, and the amacrine cells blocks the excitation signaled to the ganglion from bipolar cells.
510
What is required for the optokinetic reflex?
- The direction selective retinal ganglion cells are requires
- the optokinetic reflex stabilized moving scenes on the eye
- direction selective retinal ganglion cells sensitive to the direction of visual flow are required for this behaviour
511
Are there Direction sensitive ganglion cells in the primate retina?
Yes!
- Nearly 60 years after their first
description in rabbit retina, it
appears that DS ganglion cells have
finally been found in primate retina
512
Describe colour opponency as a building block of colour visition.
A red-on-green-off cell will increase firing to a red light covering the entire receptive field, whereas it will decrease firing in response to a green light covering its receptive field.
513
What are the 3 predominant ganglion cell types in the human/primate retina? What are the characteristics of each?
1) Parasol (magnocellular)
- luminance
- larger receptive field - motion
2) Midget (parvocellular)
- Red/Green colour opponent
- small receptive field - high acuity
3) Bistratified (Koniocellular)
- blue/yellow colour opponent
514
Describe central projections of retinal ganglion cells
- retinal ganglion cell axons leave the eye via the optic nerve and project to many different regions of the brain
- all retinal ganglion cell axons make their way to the optic chiasm, where around 60% of them cross hemispheres (project contralaterally) whereas the rest remain on the ipsilateral side.
515
Describe conscious vision
- it is generally considered to pass via the lateral geniculate nucleus of the thalamus (LGN) to primary visual cortex (aka striate cortex or V1)
516
Describe subconscious vision
- visual pathways from the retina underlie subconscious vision, which can drive reflexes, control circadian rhythm, and support subconscious visual perception
517
What is especially important for photo-entrainment of circadian rhythm?
- the hypothalamus (in particular the suprachiasmatic nucleus)
- the retinal ganglion cells that drive circadian rhythm express the photopigment melanopsin, and are themselves intrinsically photosensitive.
518
what coordinates head and eye movements to visual targets?
superior colliculus
519
Describe pupillary light reflex
- This reflex constricts the pupil in response to light
- certain retinal ganglion cells send axons to the pretectum
- pretectal neurons project to the edinger-westphal nucleus (EWN) in the midbrain
- EWN neurons send their axons via the oculomotor nerve to the ciliary ganglion
- ciliary ganglion cell neurons innervate constrictor muscles of the iris which cause the pupil diameter to decrease
- both pupils respond to monocular visual stimulation
520
What is the optokinetic reflex?
- it is a gaze stabilizing reflex
- it has a fast (saccade) and slow (smooth pursuit) component
- a subset of directionally selective retinal ganglion cells project to the nucleus of the optic tracy, which in turn leads to activation of cranial nerves controlling the eye muscles.
- blocking direction selectivity in the retina ablates the optokinetic reflex.
- even tho it is a simple reflex, it results in wide-scale activity throughout the brain.
521
What pathway underlies conscious vision?
- the primary visual pathway
- retinal ganglion cells project to the lateral geniculate nucleus of the thalamus (LGN)
- LGN relay neurons then project to primary visual cortex
522
How is visual information segregated between brain hemispheres?
- information from the right visual field projects to the left brain hemisphere
- information from left visual field projects to the right brain hemisphere
- temporal-retina-originating signals from each eye join with originating signals from the other eye at the optic chiasm
523
Does each eye have their own visual field?
- yes they have their own visual field
- combined, these produce a binocular visual field
- vision strictly in the periphery of the field of view is monocular
- due to the optics of the eye images entering the eye are flipped (both vertically and horizontally?
524
Do fibres representing superior vs inferior visual fields take different or the same paths from LGN to V1?
Different
525
Describe the visual pathways from retina to V1
1) LGN Ventral Layers:
- Magnocellular Layers: Receive input from ganglion cells with larger receptive fields.
- More transient and motion-sensitive responses.
2) LGN Dorsal Layers:
- Parvocellular Layers: Receive inputs from small receptive field retinal ganglion cells.
- Have more sustained responses and can signal color information.
3) Koniocellular Layers:
- Interdigitate between parvocellular and magnocellular layers.
- Role still unclear.
Projection to V1:
- Magnocellular Cells: Project to layer 4Cα in V1, thought to originate from parasol ganglion cells.
- Parvocellular Cells: Project to layer 4Cβ in V1, thought to originate from midget ganglion cells.
- Koniocellular Cells: Project to patches in layer 2/3 of V1, thought to originate from non-midget, non-parasol ganglion cells.
526
Receptive Field Properties in Visual Cortex
1) Classic Experiments (Hubel & Wiesel):
- Small circular spots, driving responses in retinal ganglion cells and LGN relay neurons, did not strongly drive V1 cells.
- Many V1 cells prefer elongated edges oriented at specific angles (Orientation-selective cells).
- Some orientation-selective cells respond only when a bar's preferred angle is moved across the receptive field in angles perpendicular to the long-axis (Direction-selective cells).
- Cells care about spatial frequency (size) of visual stimuli.
- Temporal frequency (speed or flicker rate) of visual stimuli is also a factor.
527
What is the the hierachical organization of the visual system?
- simple cell in the primary visual cortex
- LGN neuron / in the visual cortex, mapping receptive fields.
528
What is the architecture of the primary visual cortex?
- Much like the retina, the cortex (or
neocortex) is a highly layered neuronal
structure
- It consists of 6 layers, some of which can be
further grouped (2/3) or subdivided (4A-C)
- Incoming LGN axons predominantly
innervated neurons in layer 4C
- Superficially located pyramidal cells project to other cortical areas
- Deeper cortical pyramidal cells project to subcortical targets including the LGN and superior colliculus
529
What is the functional organization of the primary visual cortex?
- Cells immediately above and below one another in cortex represent the same location of the visual field (i.e. receptive fields are highly overlapping) and exhibit similar feature selective responses (eg. similar orientation selectivity) = orientation
column
- Cells beside one another have less
overlapping receptive fields and exhibit
different feature selective responses (i.e. there are changes in the preferred
orientation)
530
Orientation Pinwheels
1) Surface View:
- Color-coded representation of the preferred orientation of cells in the primary visual cortex.
2) Orientation Columns:
- Cells with similar orientations cluster together.
3) Orientation Pinwheel:
- In a receptive field location, all orientations are present.
4) Repeating Pinwheels:
- At the next receptive field location, orientations repeat every ~1mm.
531
Where does Binocular vision start? Describe this process.
- starts in the primary visual cortex
- Contralateral and ipsilateral retinal axons project to separate layers in the LGN
- This eye specific segregation is passed onto the input layer (layer 4) of primary visual cortex, which exhibits robust ocular dominance.
- Even outside of layer 4, though most
neurons are binocular (respond to visual stimulation of both eyes), they generally receive stronger input from one eye, corresponding to the dominance of the layer 4 inputs in their column.
532
Where does Stereopsis arise? what is it?
-thought to arise in V1
- Stereopsis is the sensation of depth that arises from viewing nearby objects with two eyes located in slightly different locations.
- Objects in front of or behind the plane of fixation project to non-corresponding parts of both retinas.
- This disparity between the two eyes
generates a sensation of depth.
- Visual cortex contains binocular ‘far cells’, ‘near cells’ and ‘tuned zero cells’ that respond maximally to different disparities between the two eyes
533
What happens after V1? (higher visual areas)
- Downstream from V1, there are several other visual brain areas that each contain a complete map of visual space.
- Higher brain regions tend to be dedicated to specific visual detection tasks.
- Middle temporal area (MT) contains
neurons that selectively respond to motion in specific directions, but doesn’t care about color.
- V4 contains a high percentage of color
selective cells, but doesn’t care about
direction of motion.
534
Describe the two streams of higher visual functions?
- The ventral stream is particularly concerned with the semantic nature of the visual scene as is referred to as the ‘what pathway’.
- The dorsal stream is particularly concerned with moving objects and is referred to as the ‘where’ pathway.
535
What is Area MT responsible for?
It is in the dorsal stream, and involved in the detection of motion.
Neurons in area MT integrate input from neurons with smaller receptive fields, so they can detect the overall direction of movement of an object.
536
What is the aperture problem?
Because V1 receptive fields are small, they may give misleading information on direction of movement. This
is referred to as the aperture problem.
537
What is the ventral stream involved in?
- the perception of color, form and object recognition.
538
What is a cataract?
- it is clouding of the lens
- they cause half the blindness (around 20 million people) and third of visual impairment worldwide
- they are most common due to aging, and risk factors, including diabetes, smoking, and prolonged exposure to sunlight
- more than 50% of americans have cataracts by the age of 80
- 1/10,000 children will develop cataracts
- cataracts can be easily removed and replaced with an artificial lens
539
what is glaucoma?
- Glaucoma is a group of diseases which
result in damage to the optic nerve and
lead to vision loss
- Around 6-60 million people suffer from
glaucoma globally (second leading cause of blindness after cataracts)
- It is most common in older adults and can have a very slow onset such that some people only notice it once a substantial amount of their vision is lost
- Leading risk factors include increased
intraocular pressure and a family history of the condition
540
What effect does mucular degeneration have on vision? what are the different types?
- In the USA, age-related macular
degeneration (AMD) is the leading cause of vision loss in people over 55, affecting ~6 million Americans
- Predominantly affects photoreceptors in the macula and fovea, affecting highresolution central vision
1) Wet AMD
- ~10% of AMD
- Arises from ‘leaky’ blood vessels
behind the retina that disturb the
connection between retina and retinal
pigment epithelium
2) Dry AMD
- 90% of AMD
- More slowly progressing than Wet
AMD, but no good treatments
- Some AMDs are also juvenile onset
541
What is retinitis pigmentosa?
- Retinis pigmentosa (RP) refers to a
heterogeneous group of largely hereditary diseases
- Affects ~100,000 people in the US
- Predominantly results in photoreceptor degeneration in the peripheral retina
- Results in night-blindness and ‘tunnel’
vision
542
What is diabetic retinopathy?
- In the USA, it is the leading cause of
blindness for people aged 20-64 and is the cause of ~12% of new blindness cases each year
- Affects ~80% of people who have had
diabetes for at least 20 years
- Retinal damage can be caused by macular edema, in which blood vessels leak their contents into the eye/retina
- In later stages, retinal damage is caused by neovascularization which leads to bleeding and inflammation
543
What happens if there is damage to primary visual cortex?
- Blindsight
- Damage to primary visual cortex (V1) can result in blindness, at least conscious blindness
- Other ‘subconscious’ forms of vision, passing via the superior colliculus (or LGN -> secondary visual areas), including awareness of visual object and visual motion, can persist
544
What is Hemispatial neglect?
- Usually arising from strokes and brain
injury occurring unilaterally in the right
cerebral hemisphere in the parietal lobe
(so the left visual field is neglected)
- Though all the visual scene is ‘seen’ by the eyes, people with certain brain injuries not only are unable to see half the visual field, they can be totally unaware of what they
are missing
545
What is Cerebral akinetopsia?
- motion blindness
- Can arise from damage to the visual
motion sensitive middle temporal area
(MT)
- Moving images appear as slowly
refreshing static images
546
What is prosopagnosia?
- face blindness
- Prosopagnosia is thought to arise after
damage to, or improper development
of, face selective visual regions in the
inferotemporal cortex (high visual areas
in the ventral stream)
547
What are some different strategies to restore vision?
1) Cell therapy attempts to use stem cells to grow and implant new cells to replace diseased or damaged cells
2) Gene therapy looks to correct damaging or null mutations via delivery of copies of the correct gene
3) Retinal prosthetic implants attempt to restore sight via implantation of an electric chip that electrically
stimulates retinal ganglion cells
4) Optogenetic therapy tries to make the remaining cells in the blind retina light sensitive
548
Describe cell therapy to restore vision
- Using stem cell approaches to generate new cells to replace diseased or damaged ones
- Can be done by growing individual cell
types in a dish and then trying to
implant them in the retina
- Could be grown as full retinal organoids in a dish, that could then be implanted to replace layers of the retina
549
Describe Gene Therapy to restore vision
- Correct damaging or null mutations via
delivery of copies of the correct gene
- Genes are delivered by adenoassociated viruses
- A gene therapy, called Luxturna, to treat a rare mutation of RPE65 was recently approved in the USA with an initial price tag of $850,000 per treatment (just approved in Canada – price currently being negotiated)
550
What are retinal prosthetic implants?
- Retinal implants attempt to restore sight via implantation of an electric chip that electrically stimulates
retinal ganglion cells
- Involves a goggle based head-worn camera system that records what enters a patient’s eyes and convolves
the visual signal into a pattern of electrical stimulation
- Approved for use in many countries (including Canada)
551
What is optogenetic therapy?
- Would work similarly to retinal implants (with a goggle based system), but could be used to make any
remaining cells in the retina light sensitive
- Involves delivery of an optogenetic channel (eg. Channelrhodopsin) to normally light-insensitive neurons
- Currently in clinical trials
- Optogenetic channels can be delivered
to different retinal neurons (ganglion
cells, bipolar cells, etc)
- Depending on the cells made
photosensitive, some normal retinal
processing (ON vs. OFF, direction
selectivity) can be restored
552
