1
Q
Neuroscience
A
study of the neurons and nervous systems
2
Q
how many neurons are in the brain and what is the power of the brain
A
100 billion neurons, and it is about 20W
3
Q
how large are neurons
A
10 microns
4
Q
Central Nervous System (CNS)
A
all the parts within bone (spinal cord, thalamus, brainstem, cortex…)
5
Q
Peripheral Nervous System (PNS)
A
not within bone (peripheral nerves)
6
Q
brainstem
A
includes the medulla, midbrain, and the pons
7
Q
spine
A
cervical, thoracic, lumbar, and sacral sections with each vertebrae numbered - can then be used to classify which parts of the skin&nerves come from where
8
Q
Neurons
A
cells with an axon that produce action potentials, are enclosed in a lipid bilayer membrane and contain organelles, but have unique morphology and they are electrically excitable - action potentials are not unique to neurons (muscle cells produce them too)
9
Q
Dendrites
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receive signals/neurotransmitters from neighbouring neurons (input) - not all neurons have dendrites but most do
10
Q
Axons
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send the signals to other neurons (output) - axons will often branch into many pathways, but only one will come off of the cell body
11
Q
Action potentials
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rapid increases and then decreases of voltage along the action potential (caused by rapid depolarization to the threshold)
12
Q
Astrocytes (CNS)
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glial cells that maintain ionic environment
13
Q
oligodendrocites and schwann cells
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glial cell that forms myelin around neurons
14
Q
Microglia
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glial cells that scavenge cellular debris
15
Q
Nissl Stain
A
piece of neural tissue is treated with a Nissl Stain solution that will dye the cell bodies of neurons - there are areas of varying density called cell layers (usually 6)
16
Q
Nissl stain showed (Nissl)
A
Nissl used basic dyes (cresyl violet, thionine) to stain the ER (RNA in the nucelus) to reveal cell bodies
17
Q
Nissl stain showed (Broadmann)
A
found that different areas of the cerebral cortex had distinct cytoarchitectonic (density of neurons) appearances (52 cortical areas, now called broadmann’s areas) - evolutionailly older cortex will have fewer layers
18
Q
cerebrospinal fluid (CSF)
A
aqueous saline solution surrounding neurons that contains sodium, potassium, chloride, and other ions in solution
19
Q
neuronal membrane
A
impermeable to the movement of ions, but ions can cross by either ion transporters and ion channels
20
Q
Ion transporters
A
active transporters (enzymes) that use energy to actively move selected ions against concentration gradients to create ion concentration gradients
21
Q
Ion channels
A
do not use energy and they allow ions to diffuse down a concentration gradient and are selectively permeable to only certain ions
22
Q
sodium potassium pump
A
enzyme that transports 3 sodium to the outside, and it transports 2 potassium to the inside using the hydrolysis of ATP - creates more sodium outside and more potassium inside and creates a concentration gradient
23
Q
neuronal membrane permeability (at rest)
A
primarily permeable to potassium because the membrane contains leak potassium ion channels, allowing potassium to diffuse out of the cell, which makes the inside of the cell negative when potassium flows out of the cell
24
Q
equalibrium potential
A
The potential at which the net flow of an ion would be zero due to electrostatic and diffusion forces being equal and opposite - still movement, but no net movement
25
Diffusion of potassium
when potassium diffuses out of the cell down its concentration gradient (outside of the cell)
26
Electrostatic force of potassium
as potassium diffuses out, the inside becomes progressively more negative, and the positive potassium is attracted to the inside
27
Nernst equation
allows us to calculate the equilibrium potential (Ex) for a particular ion (X) using the electric charge, the outside concentration and the inside concentration
28
equilibrium potentials for potassium and sodium
EK is around -84, ENa is around +67
29
Membrane potential at rest is most similar to
neuron is primarily permeable to potassium, so the resting potential is close to EK, but is not the same as the neuron is still somewhat permeable to other ions
30
neuraxis
axis of the nervous system - in humans, the neuraxis curves at the brain
31
Neuraxis before curving
dorsal is behind, ventral is infront, caudal is down, and rostral is up
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Neuraxis after curving
dorsal is up, ventral is down, caudal is back, and rostral is front
33
General axis
superior is above, inferior is below, anterior is infront of, and posterior is behind
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Midline, ipsilateral and contrelateral
line separating left and right of the entire nervous system - ipsilateral means the same side of something and contralateral means the opposite side of something
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Decussate, medial and lateral
to cross over to the other side of the brain, medial is near the midline and lateral is far from the midline
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Proximal and distal
Proximal is close to the point of reference and distal is far from the point of reference
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Efferent and Afferent
Efferent is projecting away from reference and afferent is projecting towards reference
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coronal plane
separates the front of the brain from the back (vertical axis)
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sagittal plane
separates the left from the right (vertical)
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horizontal plane
separates the top from the bottom (horizontal)
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midsagittal plane and parasagittal plane
divides the in the middle, divides into quarters
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4 rules of the nervous system
1. symmetry 2. localization of function 3. Contralaterality 4. Topography
43
Symmetry of the nervous system
when looking at a coronal section, we can see that the brain is mostly bilaterally symmetric (right is mostly the same as the left)
44
Localization of Function
different parts of the nervous system have different specialized functions, like how the different lobes in the brain all have different functions
45
Contralaterality in the brain
each side of the nervous system controls the opposite side of the body and each side of the physical field activates the opposite side of the brain
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Topography in the nervous system
there is a "map" of the body on different areas of the brain based on where each area controls
47
electric potential
when the concentration of charged ions varies on either side of the membrane
48
how was it determined that potassium is a main contributor to the membrane potential
When we record the membrane potential while altering how much potassium is in the bath around the neuron (altering concentration gradient), we find that as the potassium concentration in the bath rises, the resting membrane potential becomes more positive
49
Goldman Equation (GHK)
calculates Vm based on the concentrations and relative permeabilities of all ions crossing the membrane, which reflects the ratio of internal to external concentrations of all ions and their permeability coefficients - still a slight discrepancy due to the sodium potassium pump
50
permeability of ions
Typically, PK:PNa:PCl = 1:0.04:0.45
51
"Feeling"
Sensory stimuli evoke electrical impulse (action potentials) that travel to the brain where the stimulus is perceived - proven by local anestesia, stroke, and electrical brain stimulation
52
local anestesia
inject a blocker of voltage gated sodium channels that prevent action potential
53
electrical brain stimulation
stimulate neurons and create perception of physical sensation
54
Skin receptor cells and receptor potentials
influence axons in the skin to cause action potentials, sodium ion channels open by pressure on the skin (stretch/mechanical gates), and sodium can rush into the axon because of the concentration gradient - stronger the stimulus, the bigger the displacement and the more channels are open for longer
55
Threshold
Action potentials are only fired if the depolarization of the neuron reaches above -50mV, which causes a rapid rise and fall in the cell
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When receptor potentials reach threshold
voltage gated sodium channels open up because of the increasingly positive charge, and as the cell gets more and more positive more and more voltage gated sodium channels open in a positive feedback loop - rising phase
57
falling phase
voltage gated potassium channels detect the positive cell, and let potassium flow out so it becomes more and more negative in a slower, negative feedback loop
58
Voltage gated sodium channels activation gate
has a positive charge, it wants to open but because the inside is negative the positive gating charge keeps it shut as it is attracted to the inside - when inside gets more positive, it is able to open and as more sodium comes in, more channels will want to open
59
Voltage gated sodium channels inactivation gate
keeps swinging and eventually will swing shut, stopping more sodium from coming in
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Sodium channels closed state
activation gate is shut and the inactivation gate is open (rest)
61
Sodium channels open state
both gates are open (rising phase)
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Sodium channels inactive state
inactivation gate is closed and the activation gate is open (falling phase)
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voltage gated potassium channel creaky door
tends to open more slowly, will open when the inside is positive and there is more potassium inside than outside, as potassium then has a really strong tendency to leave the cell - falling phase
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leak channels in the falling phase
more potassium channels are open than normal which makes the permeability to potassium higher than normal, causing the voltage to get even more negative than normal (AHP)
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Afterhyperpolarization (AHP)
the hyperpolarizing phase of a neuron's action potential where the cell's membrane potential falls below the normal resting potential
66
refractory period
voltage gated potassium channels close, only the leak channels are open, and the cell returns to normal
67
Steps of an action potential
1. Depolarization past threshold by a stimulus 2. Voltage gated sodium channels open in the positive feedback rising phase 3. Sodium channels inactivate to end the rising phase 4. Voltage gated potassium channels open, causing the falling phase and the undershoot 5. Sodium channels close, ending the refractory period 6. Potassium channels close, ending the undershoot and restoring the resting potential
68
How do action potentials move down the axon? describe how they become depolarized and how they move down (sultatory conduction).
sodium diffuses along the axon, depolarizing parts of the axon that have not been depolarized yet, but not the parts in the refractory period as the voltage gated sodium channels are inactive and will not open even if they are depolarized again
69
Action potentials are like waves
have a height and they move through space. If you are not moving with it, it will push you up and drop you back down, much like the action potential does with neuron charges
70
benefit of refractory period
ensuring unidirectional action potential conduction from the point of origin
71
Consequence of refractory period
places an upper limit on the firing rate of a neuron (how many per unit time) - must wait for the voltage gated channels to close before it can fire another action potential
72
voltage clamp
placed an electrode inside the squid giant axon to monitor the voltage, and a second one to control the voltage by inject the current, and they were able to hold the voltage at a certain level to understand the opening and closing of the ion channels by examining the currents they had to inject to get to those voltages to help understand what the normal voltage was that was flowing through the axon
73
Results of voltage clamp experiments
positive charge would come in if they depolarized the neuron, but at a point they found that there was a positive charge leaving even if they made it more and more positive (sodium coming in and the potassium leaving) - eventually the sodium will not come in more because they reach the sodium equilibrium potential
74
depolarization with no sodium in extracellular fluid
no inward current but only an outward current, showing sodium causes the depolarization
75
novocaine and lidocaine
diffuse into the voltage gated sodium channel when it opens and blocks the pore, but eventually gets cleared by the blood supply - blocks the rising phase so you dont feel anything
76
Tetrodotoxin (TTX)
found in puffer fish ovaries and liver and is produced by bacteria that live in the fish, voltage gated sodium channel blocker that will not wash away and will cause death by paralysis of respritory muscles - fish has TTX-resistent Na channels (as does mammalian heart muscle) so it is not affected
77
Satitoxin (STX)
neurotoxin produced by toxic dinoflagellates in red tide, and is consumed by Butter clams and can store in fatty tissue for a year after contact (heat stable), sodium channel blocker and will cause paralytic shellfish poisoning with symptoms starting around 1 hour from consumption, including paresthesia (pins and needles numbness), paresis (difficulty moving) and respiratory difficulty
78
Why do action potentials move slowly
axons are leaky, axons are sticky, and axons are thin
79
low membrane resistance (Rm) - leaky axons
It is easy for ions to flow back out of the neuron (leak channels), so some of the ions will diffuse out - resistor is represented by the squiggly line thing
80
high membrane capacitance (Cm) - sticky axons
When ions try and move down the axon, they do not always get very far because the positive ions get attracted to what may be negative ions outside the axon (Cl-) due to electro-static attraction - capacitors are represented by the parallel lines
81
high axoplasmic resistance (Ra) - thin axons
The diameter of the axon is very thin, making it hard for the ions to flow down as there is less space
82
Invertabrates speeding up action potentials
widening their axons to get rid of the thin issue, however this takes up more room in the nervous system so not all axons can be this size
83
Vertabrates speeding up action potentials
evolved myelin to blocks the leakiness and the stickiness
84
Myelin
fatty lipid insulator, which coats thin axons - plugs the leak channels and distances the inside and outside charges
85
Nodes of Ranvier
potassium and sodium still need to come in, so the myelin is interrupted by the Nodes of Ranvier, areas with no myelin where the voltage-gated sodium and potassium channels are concentrated
86
saltatory conduction
action potential "jumps" from node to node rapidly, but the nodes allow the action potential to regenerate
87
Oligodendrocytes
Type of glial cell in the CNS that wrap axons in a myelin sheath - will myelinate more than one axon
88
Schwann cells
Type of glial cell in the PNS that wrap axons in a myelin sheath - can only wrap around one axon but wrap around axons numerous times
89
How myelinating glial cells function
wrap themselves around neurons in order to give the axons myelin, "squeezing" its membrane down, to squeeze its own cytoplasm back out
90
Multiple Sclerosis
damage to the myelin in mainly the CNS, which can be replaced and continually damaged, thought that the immune system makes a mistake and the antibodies attack the CNS myelin. The first symptoms (vision, tactile, balance, speech) usually occur between 20-40. 2x as common in women then men, (1/1000 people). Genetic factors play a role in susceptibility. Many different areas may be affected, but feel fine the next day when the myelin gets replenished
91
Gullian-Barre syndrome
Similar to MS but occurs in the PNS, causing paralysis, paresthesias, loss of sensation, movement difficulties, and difficulty breathing (30% of patients require a respirator). It has rapid onset (days), but recovery can take only a few weeks or years - very rare (1/100 000 people)
92
Cajal using the golgi stain
hypothesized that neurons were unique individual cells
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synaptic cleft
very small gap between
94
different areas may be affected, but feel fine the next day when the myelin gets replenished
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synaptic cleft
very small gap between pre and postsynaptic neurons (20 nanometers)
96
Loewi
knew that if he electrically shocked the vagus nerve the heart would slow down, so he used two hearts in beakers of saline that were connected to eachother via a tube, and he simulated the first nerve, finding that heart 1 and 2 slowed down even though he only ever stimulated heart 1 - inferring the existence of neurotransmitters
97
Quantal transmission of neurotransmitters
quantity of neurotransmitters in a vesicle are released (they do not leak out) - stimulated an axon (1 or 2 axon potentials), and saw that the amplitudes of depolarization were discrete (a multiple of 0.4mV)
98
synaptic bouton/axon terminal
bulge at the end of the presynaptic axon that carries packages (synaptic vesicles of neuronal membrane) filled with neurotransmitter molecules
99
postsynaptic dendrite
has receptors for the neurotransmitters
100
Synapse at rest
presynaptic neuron has the neurotransmitters inside it, with a voltage gated calcium channel that is closed - calcium concentration out of the cell is quite low, but it is super super super low inside the neuron, so there is a strong gradient favouring calcium coming in
101
Synapse at action potential
opens and calcium invades the cell, eventually causing the release of the neurotransmitter, neurotransmitters diffuse across the cleft, and attach to the proteins that make up the receptors, opening up their own ligand-gated ion channels that affect the postsynaptic neuron
102
calcium pump
use ATP to pump calcium out of the cell (similar to sodium potassium pump), and will pump hydrogens in
103
sodium calcium ion exchanger
does not use energy directly, but takes advantage of the fact that sodium is higher outside than inside, using the energy of sodium coming in to put calcium out - Indirectly powered by sodium potassium pump
104
Synaptotagmin
calcium detector which will bind to calcium, SNARE proteins will then pull the vesicle membrane and synaptic membrane together, and calcium bound synaptotagmin catalyzes membrane fusion
105
Neurotransmitters
chemical molecules, including Glutamate, GABA, and Glycine (small molecule transmitters) - Glutamate is most common excitatory, GABA is most common inhibitory in the cerebral cortex and Glycine is another common inhibitory
106
glutamate receptor channel
binds glutamate to receptors on the channel, opening the channel it is connected to to let sodium rush in - ionotropic ion channel. Channel is equally permeable to sodium and potassium, so potassium can also flow out as sodium flows in. This is an excitatory postsynaptic potential (EPSP), it has the potential to reach threshold and fire an action potential
107
GABA receptor channel
binds GABA and the channel opens, but it is selectively permeable to chloride which will enter because of its concentration gradient and hyperpolarize the cell - inhibitory postsynaptic potential (IPSP) which makes it even harder to reach threshold
108
driving force equation
describes how much ion will flow into the cell when the receptor channel opens, Ix is the current, which is equal to the conductance of the membrane for ion x (gx), multiplied by the membrane potential minus the equilibrium potential for x
109
current
positive current means ions flow outwards and the cell loses positive charge or gains negative charge. Negative current means the ions flow inwards, the cell gains positive charge or loses negative charge
110
axon hillock
axon and cell body meeting place, where action potentials are first fired and threshold needs to be met
111
Patch clamp (cell attached)
glass pipette and a small amount of suction creates a tight seal so that all the ions that flow when an ion channel opens must go through the pipette and be measured by an electronic amplifier. Response characteristics of different channels can therefore be compared
112
whole cell patch clamp
strong suction breaks the membrane and the pipette becomes continuous with the rest of the membrane
113
Inside out patch clamp
removing the pipette in the cell-attached configuration, removing a small vesicle of membrane that has its intracellular surface exposed when the tip is exposed to air. This allows of the measurement of single channel currents, and makes it possible to change the medium of which the intracellular surface is exposed to
114
outside-out patch clamp
removing the pipette in the whole cell configuration, the ends will anneal and the extracellular surface will be exposed. This allows us to study how single channels are affected by extracellular environments
115
spatial integration
Synapses can occur on different parts of the dendritic tree at the same time, and the EPSPs combine as spatial integration, making it easier to hit the threshold - EPSPs closer to the axon hillock are stronger as they do not need to diffuse as far
116
temporal integration
synapse can fire a number of action potentials in a row in temporal summation, which decline as a function of time but can sum up to meet threshold
117
Dermatones
imaginary mappings on the body surface that are from that particular spinal segment
118
transverse section of the spinal cord
spinal cord consists of grey (inside in the shape of horns) and white matter, grey matter does not have much myelin (mainly cell bodies and dendrites), but white matter is almost exclusively myelinated axons - lumbar/cervical sections have large ventral horns (involved in motor function), but they are small in the thoracic section
119
axons from the finger
Ab, Ad and C axons branch from the dorsal root ganglion, where the peripheral branch goes to the finger and the central branch will enter the spinal cord through the dorsal horn
120
Abeta axons
touch/pressure/mechanosensory afferent fiber - enters the spinal column, but turns and goes up rostrally, larger diameter and travel faster
121
Adelta and C axons
pain and temperature afferent - enter the dorsal horn, and synapse onto the second order neuron, which crosses to the ventral part of the cord and then goes rostrally, Adelta are smaller in diameter, C are smallest and not myelinated
122
Dorsal Column Medial Lemniscus Pathway (DCML)
Upon entering the dorsal column, Ab axons turn and travel rostrally ipselaterally through the white matter towards the brainstem. When reaching the caudal medulla, in the dorsal column nuclei, they synapse onto a second order neuron that decussates, and goes rostrally to the thalamus, then synapsing onto more neurons that bring the signal to various places, including the parietal cortex (S1) - the decussation in the caudal medulla is the the medial lemniscus
123
spinothalamic tract (STT)
Ad and C axons enter the dorsal horn and synapse onto a second order neuron which decussates to the ventral part of the white matter where it then travels rostrally. They travel to the thalamus, where they synapse and then travel to various places including the parietal lobe (S1).
124
topography of DCML
axons from caudal parts of the body will go as far medial as they can, before going up rostrally - the most caudal axons will be the most lateral in the dorsal column
125
topography of STT
Axons from caudal places synapse in the dorsal horn, and the second order neuron goes as lateral as possible
126
Brown-Sequard Syndrome
damage to white matter of the person's left or right side spinal cord, results in ipsilateal loss of touch and contralateral loss of pain and temperature
127
Mechanotransduction
process by which the nervous system converts physical pressure on the skin to an electrical signal
128
cross section of a finger
as you go down, you find specialized receptors called Meissner corpuscle, then Merkel cell-neurite complex, then Ruffini endings, and Pacinian corpuscles, and free nerve endings for the Ad and C, which are connected to axons (usually Ab)
129
microneurography
person allows an electrode to be inserted into the skin into an axon (ab), and they can tap on the skin with a probe, listening to the oscilloscope until they find the receptive field
130
receptive field of Meissner and Merkel
very small, as these cells are close to the surface of the skin
131
receptive field of Pacinian and Ruffini
larger receptive field, as they are further below
132
Meissner
responds best to low frequency vibrations (2-50Hz)
133
Pacinian
responds to high frequency vibration (over 50Hz)
134
Ruffini
responds to skin stretch
135
Merkel
static indentation of the skin
136
receptor adaptation
if you give a constant indentation, they do not give a constant rate of firing
137
Meisner and Pacinian adaptation
will adapt fast, and will only respond multiple times when you indent, unindent and then indent again
138
Merkel and Ruffini adaptation
will continue to fire action potentials, but in the static phase they will be much lower firing rate
139
Merkel cells structure
contains neurotransmitters and voltage gated calcium channels - not a neuron as it does not fire action potentials or have dendrites
140
when the skin is pressed
mechanically gated ion channels of the Ab axon will open and let sodium in (dynamic phase), but channels will close if the skin is held indented
141
At the same time, mechanically gated cation channels of the Merkel cell
will also let sodium in, depolarizing the Merkel cell, opening the calcium channels, and releasing neurotransmitters that bind to receptors on the Ab axon - but this is a slow firing phase accounting for the static phase
142
two point test
calipers can be opened and pressed at two points, and a patient must say if they feel one or two points - can find out what the smallest distance is between the points for the participant to know they are two points (two point threshold) - neurons will fire the most when they are touched in the centre compared to the edges
143
receptive fields and the two point test
When the brain receives much stronger signal from neuron B than A and C, it makes an inference that because more action potentials come from axon B that it is only being touched by one thing from axon B - patient will feel two points if the firing rates of A and C respectively are higher than B
144
Adaptation benefit
helps us ignore constant, innocuous stimuli, reducing distraction and helps to avoid saturation of neural firing rates, allowing us to detect change in stimulus intensity over a larger range of intensities
145
adaptation and neural stimulation
As the strength of a stimulus increases, you get more and more action potentials, but you eventually hit a maximum - adaptation avoids us hitting this, which is important because if two stimuli would be under this max part, we would not be able to distinguish this without adaptation lowering the firing rate
146
consequence of adaptation
we can no longer tell exactly how hard something is pushing on the skin (we do not know if it was adaptation or a stimulus that is not adapted and is weaker) - we are good at detecting changes, but we are bad at knowing the intensity of a stimulus
147
somatosensory cortex (S1)
4 different areas in the post-central gyrus, 3a, 3b, 1, and 2 - these are some of broadmans areas. 3a is mainly proprioceptive (knowing where limbs are in space), 3b is light touch with small receptive fields, 1 is light tough with large, multi-digit receptive fields, and 2 is proprioceptive and light touch. 3b is the most "important"
148
somatosensory homunculus
Each area has a parallel somatosensory homunculi that look basically the same. The areas of the body with the most receptor density are magnified as they have more neurons devoted to those areas
149
somatotopic representation in rats
whiskers are extremely sensitive, and they use them to make fine discriminations, in the ratunculus each whisker follicle has its own group of a few thousand neurons organized somatotopically, but contralaterally due to the cross-over - look like barrels
150
somatosensory map plasticity
when a monkey looses a finger, in the homunculus the area for that finger acquires input from the neighbouring areas, so the areas for fingers 2 and 4 become larger - digits don't get more sensitive, as the neurons in the skin have not changed
151
phantom limb sensation
When an entire arm or leg is amputated, often the homunculus does not fill in completely, so there are neurons which do not change and can fire action potentials on their own, the brain assumes the limb is receiving input
152
Extracellular recording
using a metal microelectrode that is inserted next to a neuron in an animal brain in vivo and connected to an oscilloscope and an audio amplifier - action potentials can still be recorded, but they will be in "reverse" because as Na enters the cell, the outside becomes slightly more negative, signals are much weaker as there is no accumulation of charge in extracellular fluid
153
use of extracellular recording
used to map the homunculus of monkeys - inserted the electrode individually in different areas, and drew out maps of the receptive fields of the neurons on the hand on the cortex of the monkey, and discovered the cortical column
154
cortical column
as he moved his electrode down from the surface of the brain towards the end of the cortex, the receptive fields were very similar, leading to the discovery of the cortical column
155
Temp and pain receptors at the skin
received through free nerve endings which are typically quite close to the skin - do not have specialized cells, but they have specialized receptors (thermoreceptors)
156
warm and cold receptors
when the skin cools off the firing rate reduces, and when it gets warmer it increases, and when it is held constant it adapts - cold receptor is the opposite but still adapts
157
Transient receptor potential V1 receptor (TRPV1)
opens/fires due to warmth, permeable to Na and Ca - chilli peppers feel hot when we taste them even when they are not physically hot, this is due to capsaicin which can cross the lipid membrane of the axon and bind to the TRPV1 receptor on the intracellular domain, causing the receptor to open
158
Transient Receptor Potential M8 receptor (TRPM8)
cold receptor that is permeable to Na and Ca - mint tastes cold due to menthol being able to bind to the TRPM8 receptor, causing it to open
159
Referred pain
when one of the internal organs is getting a stimulus that should cause pain, which is felt not in the organ, but on the skin surface elsewhere
160
what causes referred pain
convergence - different presynaptic axons from different parts of the body can synapse in the same area, when skin and intestine neurons synapse pain signals on a specific neuron, the brain infers that pain is coming from the skin even when the pain signal is coming from the intestine neuron because the skin one fires more
161
why do we rub the body when we knock it on something
Ad and C axons synapse on the projection neuron in the dorsal horn, Ab comes in and leaves, but it also branches and synapses inside the dorsal horn on an interneuron - when you rub your skin, it releases glutamate onto this interneuron, which releases GABA or Glycine (both inhibitory), which will synapse on the dorsal horn projection neuron, causing IPSPs, reducing the number of action potentials
162
Light pathway
goes through the lens (lens and cornea) and is focused onto the photodetector layer (retina) on the back of the eye
163
vitreous humour and aqueous humour
fluid that is behind the lens, and
164
Explain how A-beta axons reduce the sensation of pain?
comes in and leaves, but it also branches and synapses inside the dorsal horn on an interneuron - when you rub your skin, it releases glutamate onto this interneuron, which releases GABA or Glycine (both inhibitory), which will synapse on the dorsal horn projection neuron, causing IPSPs, reducing the number of action potentials
165
vitreous humour and aqueous humour
fluid that is behind the lens, and in front of the lens but behind the cornea
166
muscles of the eye
iris (coloured part) which controls the size of the pupil (opening that lets light through), and those which control the bending of the lens
167
fovea
pit in the retina and is where we have many cones for the finest acuity
168
emmetropia
normal vision - point of light will fall on the retina like a point due to correct refraction from the cornea
169
Myopia
focal point is in front of the retina because the eyeball is too long or too curved (nearsighted)
170
Hyperopia
focal plane is behind the retina because the eyeball is too short or the cornea is not curved enough (far sighted)
171
Snell's law
n1sinθ1 = n2sinθ2 - density changes the speed of light in the substance, causing refraction
172
why does the cornea do most of the focusing
ratio of Ncornea and Nair is about 1.38, ratio of Nlens and Nwater is smaller so the lens has harder time bending the light compared to the cornea
173
presbyopia
as we age, the lens gets less flexible
174
images on the retina
upside down and left right inverted, but the brain corrects for this
175
backwards organization of the retinal layer
photoreceptors are on the bottom of the retina, then the bipolar cells in the middle, and the retinal ganglion cells on the top, but the photoreceptors are the ones which absorb the light
176
blind spot
the 1M retinal ganglion cell axons have to plunge through the retina, taking up a lot of space, which produces a blind spot where there are no photoreceptors (see a white circle due to myelin reflecting light back, called optic disc)
177
why are we unaware of the blind spot
there is one in each eye, so they are almost never looking at the same spot, and the brain perceptually fills in whatever is in the blind spot
178
Photoreceptors, Bipolar cells, ganglion cells
receive the light, receive transmitters from the photoreceptors, receive from the bipolar cells and have axons
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retinal pigment epithelium cells
back layer of the retina, absorb light that is not absorbed by photoreceptors so it doesn't bounce back, and they nourish the photoreceptors which are in contact with the cells
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pulse-chase experiment
radioactive amino acids which were taken up by the photoreceptor terminals over time migrated upwards towards the pigment epithelium, eventually landing in the retinal pigment epithelium
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why did the amino acids migrate
Vision requires transparent surfaces, and photopigment, which is housed in the discs, is eventually damaged, so the discs constantly migrate towards the pigment cells, get shed, and dew disks are made
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shedding of discs
occurs through phagocytosis, where the discs are pinched off and taken into the retinal pigment epithelium
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Phototransduction
process of converting light into APs - photoreceptors are very much like neurons, but are not neurons as they have ion channels and release transmitters, but do not have axons/APs
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photoreceptors in the dark and light
inward current (dark current, -40mV) which is reduced by the light (-65mV) - light causes hyperpolarization
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photoreceptors in the dark
cGMP is bound to the intracellular side of the sodium-calcium channel, opening the channel so sodium and calcium can enter, and potassium can leave
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photoreceptors in the light
potassium still leaves, but cGMP diminishes with the intensity of the light, closing the sodium calcium channel, hyperpolarizing the cell
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photoreceptors neurotransmitter release
Photoreceptors release glutamate when calcium binds, but when the cGMP is degraded and calcium cannot come in, neurotransmitter release is diminished
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photoisomerization
Retinal (in opsin) is a form of vitamin A that has two isomers, and it changes shape when light hits it
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results of photoisomerization
activates transducin, which activates phosphodiesterase (PDE), which degrades cGMP, and the cGMP channels close - more intense light causes more photoisomerization and more cGMP is destroyed
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Guanylate cyclase
produces cGMP and is inhibited by calcium - in light, calcium decreases, so guanylate cyclase activity rises and cGMP production increases, and the channels open, letting calcium back in (adaptation)
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the optical illusion in class
When you look at light for a long time, photoreceptors adapt, and then when you look at light again they will respond less to the light - parts that were previously in the dark were not adapted, so they respond more to the light when presented with light
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Opsin
changes the physics around the retinol to determine which wavelength of light it responds to
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rods and cones
photoreceptors - one type of rod, but 3 cones which are dependent on their opsin
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types of cones
respond best to short (blue), medium (green) and long (red) wavelengths of light - responsible for colour vision, have better spacial acuity (less convergence) and see in finer detail (fovea is packed with cones), 2x more
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rods
longer and contain more photopigment than cones, and are therefore more sensitive - responsible for grayscale vision (light intensity)
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why are rods more sensitive
have a better chance of absorbing light in dim light, many rods will also converge onto the same bipolar cell meaning a rod bipolar cell is much more sensitive to light than a cone bipolar cell (receives more input), have greater amplification as they close more sodium channels in response to the same amount of absorbed light
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why is the fovea packed with cones
this means it lacks overlying axons and blood vessels to reduce light scattering
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determining the placement of cones
can be determined by flashing a certain colour of light and examining the retinal placement - found there are fewer blue cones than red and green cones
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Retinal ganglion cell
exist in different types, but they tend to respond best to light/dark spots in the centre of their receptive field - can be on-centre or off-centre
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On-centre retinal ganglion cell
fires when light is on the centre - have a metabotropic glutamate receptor (mGluR6)
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Off-centre retinal ganglion cells
fires when centre is dark - have normal glutamate receptors
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Glutamate in the mGluR6
is inhibitory and cases sodium channels to close - glutamate is released when photoreceptors are dark, so on-centre bipolar cells are inhibited in the dark while off-centre are activated in the dark
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sign inverting synapse
synapse that changes the sign at the other synapse - off-centre is positive since cones and the bipolar cell do the same thing, while on-centre is negative since mGluR6 makes them do opposite things
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ionotropic receptors
ligand itself opens the channel by binding to the channel - ligand-gated
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metabotropic receptors
has the receptor bind, activate enzymes that then inhibit or activate, so they are slower but can have wider effects
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Biolistic transfection
coating gold particles with DNA, loading them into a gene gun, and then shooting them into cells in vitro - gold is heavy and will insert itself into the nucleus of the cell
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uses of biolistic transfection
DNA that encodes fluorescent proteins can be shot in, allowing visualization of structures and functions (cell will produce more of the endcoded protein), and computer programs can be used to process the images
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enkepgalinergic neurons
cause a reduction in pain by synapsing with nociceptive axons, releasing enkephalin to inhibit their release of neurotransmitters onto projection neurons
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types of axonal transport
slow axonal transport (0.2 - 8mm/day) and fast axonal transport (200-400mm/day)
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directions of axonal transport
Retrograde is transport towards the cell body, and anterograde is transport towards the axon terminal
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types of refractory periods
absolute and relative, voltage gated Na channels are inactive, then they are active but the cell is hyperpolarized
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Golgi stain
a neural stain that completely darkens a few of the neurons in each slice of tissue
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central vision
parts of the visual system that are in the CNS
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Surround cones in the dark
release glutamate onto GABAergic horizontal cells which depolarize and release GABA onto the centre cone, causing it to hyperpolarize, like if it got more light - more contrast makes you more visual.
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horizontal cells
mediate horizontal interactions in the retina
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Colour opponency
centre and surround cones can be different colours - red-green, green-red, and blue-yellow
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left or right monocular visual field
what the left or right eye sees - they are not entirely the same (left extends farther to the left, right farther to the right)
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monocular/binocular portions
The parts that only one eye sees/the parts that overlap
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Nose and the visual field
The bottom internal corner of both visual fields also gets cut off by the nose, but the binocular visual field is able to fill this in
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Left or right visual field
everything to the left or right of the fixation point - different from left or right monocular visual fields
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Contralaterality of vision
Everything in the left visual field activates the right occipital lobe - caused by the decussation of the nasal retinal axons at the optic chiasm
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Amplification of vision
magnification of certain regions in the visual field - those near the centre take up more area in the occipital lobe
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Topography in vision
each part of the visual field can be mapped onto the occipital lobe
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Optic nerve and optic tract
optic nerve (CN II) is the axons from one eye, optic tract is axons from both eyes - all of the axons in each optic tract are getting input from the contralateral visual field
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superior colliculus
calls attention to quick movement in the periphery
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Superchiasmatic nucleus
part of the hypothalamus, close to the optic chiasm, involved in our circadian rhythms (we know to sleep at night and get up in the morning)
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pretectum
involved in the pupilary constriction reflex (pupils constrict when light increases)
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lateral geniculate nucleus (LGN)
part of the thalamus and is where the optic tracts feed to, then axons go to the primary visual cortex (V1, Broadman's area 17, striate cortex)
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anopsia
Blindness not in an entire eye
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Hubel and Wiesel LGN experiment
spot of light was projected onto a screen, and a cat is placed in front of it with it's eyes focused on the screen and an extracellular recording electrode inserted - when the electrode was in the LGN, they found a spot of light in the receptive field would cause action potentials (receptive fields of LGN cells are very similar to retinal ganglion cells)
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Hubel and Wiesel V1 experiment
Found spots of light didn't produce much of a response, but cells respond very well to bars of light angled at a specific degree (orientation-selective neurons) - many had simple orientation structures (simple cells with a bell shaped firing rate as you rotated the bar
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orientation columns (Hubel and Wiesel)
in a coronal section of the cerebral cortex (has 6 layers), the neurons had the same preferred orientation as you go down, but if you go to the side it shifts like the hands of a clock - these are the orientation columns
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How are the orientation-selective receptive fields of V1 neurons formed from the circular repetitive fields of LGN neurons
Multiple LGN neurons send axons to the same V1 neuron, so the V1's receptive field is created by a process of spatial summation, specifically the centre that sums to a bar shape - a bar of light in the right direction would cross over all of the centres of the LGN neurons
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ventral view of the LGN
on either side it consists of 6 cell layers, each either ipselateral temporal axons or contralateral nasal axons (cont, ips, ips, cont, ips, cont) - neurons in the LGN only receive input from one of the two eyes, never both
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ocular dominance columns
Cortical columns consisting of neurons that receive signals from the left eye only or the right eye only - LGN neurons send their axons to the V1 (optic radiation), which terminates in layer 4 of the primary visual cortex where the eyes are segregated (above and below layer 4 there is some mixing, but it is mainly segregated)
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ocular dominance columns electrode experiment
Extracellular electrodes were inserted in oblique electrode penetration (very shallow angle) so that they could cross over multiple columns - found that as they advanced the electrode across, one eye would drive the neuron with more action potentials in most neurons, and it was a gradient where all the neurons would respond to the right eye, then go slowly towards equal, then slowly towards the left eye, then back to equal
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glutamate photo-uncaging
brain is bathed with caged glutamate, (glutamate attached to a compound that "cages" it, preventing the binding site on glutamate from binding to the receptor) and is flashed with UV with a specific wavelength, breaking the bond to the caging compound (focal photolysis) so the glutamate can bind to the receptors and cause action potentials
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Photo-uncaging use
coronal slice of the cortex was taken, and a whole cell patch-clamp was attached to a specific neuron while UV light was used to uncage glutamate at many different positions - only some positions caused activity
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Binocular disparity
fixation point falls on the fovea, an object further away will falls more nasal, the angle between the light rays that are closer is larger than that of the fixation point (near disparity), light rays at the same depth but more left in space land more temporal in the right eye and more nasal in the left
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Higher visual areas
get input from the visual cortex, and they are located all over the brain, serving many different functions
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MT/V5
"where" pathway, also known as the dorsal (spacial) stream - involved in knowing where things are in the world
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V4
"what" pathway, also known as the ventral (object recognition) stream - involved in detailed vision for identifying objects or learning details of objects
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cerebral achromatopsia
colour blindness caused by damage to V4, not the actual cones or eyes, causing loss of all colours
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cerebral akinetopsia
loss of the ability to perceive movement caused by MT damage
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MT neurons
have preferred motion direction, similar to simple cells (but for motion)
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waterfall illusion
thought to be caused by adaptation of the V5 neurons that respond best to downward motion - when the video stops, the downward motion neurons have lower firing rates, so the waterfall appears to go upwards
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Sound
wave that travels through air - alternating compression and rarefaction of air particles (longitudinal wave)
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Higher frequency
generally means a higher pitched sound, although pitch is a percept (much like colour) - it is not a perfect correlation to the frequency
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Sound localization
allows us to determine where things are that are making sounds - done by the loudness of the sound (if it is louder in one ear than the other) and the time of arrival of the sound (will hit one ear before the other if it is not coming directly in front or behind)
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Auditory
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Auditory axons pathway
Cochlear nerve from the spiral ganglion enter the rostral medulla of the brainstem. Here, the dorsal cochlear nucleus sends axons which decussate and then go to the inferior colliculus of the midbrain, which go to the auditory thalamus, then the auditory cortex. The ventral cochlear nucleus sends axons to the pons. This pathway is bilateral (activate the left and right auditory cortex)
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tonotopic organization
mapping of frequency in the auditory cortex that corresponds to the mapping of the cochlea, where each neuron responds to different frequencies
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lateral superior olive (LSO)
allows us to tell sound intensity between the two ears by determining which ear is louder and by how much
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sound shadow
In general, any object will at least partially block sounds with wavelengths smaller than that object (for humans, sounds that are greater than 2000 Hz are blocked by the head)
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Cochlear nucleus and the LSO
Each cochlear nucleus activates the ipselateral LSO, but also has decussating axons that activate the contralateral MNTB, which has inhibitory interneurons activated by the glutamate from the cochlear axons, releasing inhibitory neurotransmitters onto their ipselateral LSO (contralateral to cochlear nucleus)
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medial superior olive
monitors interneural time difference for low-frequency sounds - sounds coming directly from one side have the largest delay from ear to ear, sounds directly in front/behind of you have no delay
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jeffress model
Sounds hit the left ear before the right and cause action potentials which go to each MSO, the distance traveled being systematically varied. The same neurons in each MSO receive neurons from both ears - so, the axons from the left ear will go farther in the same time as the axons from the right, releasing glutamate onto more neurons, but the neuron receiving glutamate from both ears is the only one that fires via spatial summation
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external ear
concha, pinna and external canal - funnels sound into the tympanic membrane
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ossicles of middle ear
malleus, incus, and stapes, attached to the tympanic membrane
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sound in the ear
vibrates the tympanic membrane, causing the ossicles to move, pushing the oval window in and out, causing fluid in the ear to vibrate
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acoustic attenuation reflex
when the tensor tympani and stapedius muscles contract, the ossicles cannot move as easy - reflex that happens to protect the ears when exposed to very loud noise, may happen when we speak as speaking vibrates our skull and would be very loud
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eustachian tube
connects the middle ear to the throat so the middle ear pressure can be the same as the external pressure - tympanic membrane is very delicate, so if the internal pressure is different from the external pressure, it pushes the membrane in or out and it cannot vibrate as well
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Amplification in the ear
oval window is much smaller than the tympanic membrane, thus force is funnelled to a smaller area, increasing pressure (stapes displaces the oval window with 1/10 the displacement of the tympanic membrane, but with greater force) - ossicles are a mechanical advantage lever system to increase the force
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cochlea
coiled (when it is uncoiled it is 32mm long) and contains perilymph fluid which is displaced when the stapes vibrates
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round window
counteracts the displacement of perilymph in the cochlea
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basilar membrane
narrow (150 microns) at the base of the cochlea and is for high frequencies, while it is wider (500 microns) at the apex and is for lower frequencies
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cochlea tonotopic organization
When the fluid vibrates, the particular part of the basilar membrane of that frequency vibrates and resonates - basilar membrane sends axons from each part to the cochlear nerve
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Conductive hearing loss
vibration is prevented from reaching the inner ear - caused by packed wax, otitis media, or otosclerosis
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otitis media
infection of the middle ear that enter through the throat and causes pus build up that dampens vibration - common in kids as the eustation tube is shorter and more horizontal, making it harder to drain, can be drained or antibiotics
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otosclerosis
stapes gets fused to the bone around the oval window and it cannot vibrate, can be treated surgically
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Sensorineural hearing loss
neural processing is compromised - includes occupational deafness, presbycusis, antibiotic ototoxicity (antibiotics damage hair cells), and acoustic neuroma
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occupational deafness
when someone words in a loud environment with no ear protection, vibrating the basilar membrane too much breaking the hair bundles
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presbycusis
loss of hearing in the high frequency range with age due to damaged hair cells
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Acoustic neuroma/vestibular schwannoma
tumor built up on the 8th cranial nerve in the vestibular schwann cells
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Antigens
proteins that are detected by antibodies (have a tail region and a binding site for the antigen)
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direct immunofluorescence
primary antibody tail region is fluorescently tagged (anti-A), it will then bind to antigen A and A can be detected when bound
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indirect immunofluorescence (better)
tail regions of antibodies are conserved, so anti-A can be made in the rabbit, and then labelled goat anti-rabbit can be used to bind to the rabbit anti-A (can inject rabbit antibodies in goat bloodstream, body makes them) - less laborious and allows for amplification as several secondary antibodies can bind to the same primary antibody tail (stronger fluorescence)
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Immunofluorescence for mice and sound exposure
immunofluorescence for synaptic ribbon protein (labels hair cell nucleus and synaptic terminals) and heavy neurofilament protein (auditory nerve axon) revealed disorganization of IHC nuclei and reduced synapses
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Organ of Corti
Center part of the cochlea, containing hair cells, canals, and membranes
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Sections of the cochlea
scala vestibuli, scala media, scala tympani
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hair cells
specialized auditory receptor neurons embedded in the basilar membrane and have their hair bundles embedded in the tectorial membrane
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Endolymph
fills scala media, high in potassium
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perilymph
fills scala vestibuli and scala tympani, low in potassium
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When basilar membrane bounces
inner hair cells bounce, hair bundle is pushed into the tectorial membrane, creating a shearing force in the horizontal - very sensitive to movement
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stereocilia of inner hair cells
organized based on size (get progressively taller), contain cytoplasm, voltage gated calcium channels and synaptic vesicles with glutamate
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tip links/gating spring
connect the tips of hairs, gate the ion channels and have mechanically sensitive ion channels
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shearing force and tip links
increases the tension connecting the tip links, which physically pulls open the ion channel, ions in the endolymph (potassium, calcium) enter and depolarize the cell, causing voltage gated calcium channels to open, allowing glutamate release
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Direction of hair bundle deflection
one direction causes depolarization, the other causing small hyper polarization - decrease the tension which may possibly close a channel that was not fully closed
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outer hair cells (cochlear amplifier)
depolarize and shrink during bounce, pulling the tectorial membrane down and the basilar membrane up, amplifying the resonation of the basilar membrane
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prestin
motor protein on the OHC membrane
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Roll, Yaw, Pitch
rotation around the x axis, rotation around the z axis, rotation around the y axis - all specifically in relation to the head
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3 semi circular bony canals
anterior, posterior and horizontal canal - attached to the same bone as the cochlea, contain endolymph, are mutually perpendicular, designed to detect rotation in their own plane
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vestibular system
The sensory system that responds to gravity and keeps people informed of their body's location in space.
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two otolith organs
utricle and the saccule - little bulges in the bone that detect movement in a linear fashion and tilt
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otolith organ structure
contain hair cells and support cells, hair cells are embedded in otolithic membrane with otoconia on top - striola is midline
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Tilt/linear movement
gravity pulls down on the otolithic membrane as the otoconia add mass for the gravity to act on, hyperpolarizing some hair cells and depolarizing others
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head tilt adaptation
tip-links are fixed to myosin which is moves up the actin of the stereocilia, increasing the tension and opening the channels to let potassium and calcium in - when calcium increases, it causes the tip-link motor to slip off the actin, reducing the tension by falling
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Cupula
gelatinous substance in which hair cell bundles are embedded in the semicircular canals
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Ampulla and Crista
bulge in the bony canal and an epithelial cell layer in which the hair cell bodies are embedded
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rotation
head and the cupula move, but the fluid is not getting moved as fast (inertia) so cupula is deflected backwards
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rotation adaptation
dramatically adapts back to baseline - during sustained rotation, endolymph in the semicircular canal "catches up" to the speed of rotation, meaning the cupula is no longer deflected
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Scarpa's ganglion
vestibular ganglion
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vistibulo-ocular reflex
brain discovers how fast the head is moving, the eyes automatically rotating so whatever you are looking at stays still
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VOR pathway
When the head turns to the left, axons from the left horizontal semicircular canal enter thru scarpas ganglion and synapse in the medulla, which goes to abducens nucleus in the pons. Abducens nerve will go to the right lateral rectus, which releases ACh that causes the muscle of the eye to contract in the rightward direction. The pons also sends signals to the midbrain and synapses onto the oculomotor nucleus which activates the medial rectus of the left eye, also causing a contraction to the right
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Oscillopsia
bilateral loss of the VOR, causes apparent motion of objects and blurring of vision which can result when hair cells are destroyed by medications
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Benign paroxysmal positional vertigo
otoconia from the utricle get dislodged and enters the posterior semicircular canal, so in certain head positions they smash against the cupula and make the person feel very dizzy
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Positional alcohol nystagmus
alcohol enters the cupula, making it lighter than endolymph, so it becomes more buoyant and deflects in certain head positions
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primary motor cortex
in the frontal lobe and is just rostral to the central sulcus (contains broadmans area 4) - directly involved in controlling movement, similar in most mammals when scaled to body weight
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premotor cortex
rostral to primary motor cortex (contains broadmans area 6) - involved in the planning of complex sequential movements, larger in humans when scaled to body weight
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apraxia
loss of ability to plan and execute complex and voluntary motor movements, results from prefrontal cortex damage
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corticospinal tract
Axons from layer 5 of the cortical column send their axons to the spinal cord, controlling the extremities - can be split into lateral and ventral
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corticobulbar tract
Axons from layer 5 of the cortical column send their axons to the brainstem, controlling the muscles of the face
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lateral corticospinal tract
axons decussate in the caudal medulla, then continuing descent in the lateral white matter of the spinal cord, synapsing in the ventral horn onto lower motor neurons, causing limb movement (distal muscles)
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ventral corticospinal tract
no decussation, axons continue descent in the ventral white matter, eventually going bilaterally to synapse in the medial part of the ventral horn, causing axial/proximal muscle movement
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lower motor neurons
ventral horn motor neurons, innervate skeletal muscles
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Upper motor neurons
involved in controlling movement that do not go to muscle cells by themselves - send their axons to the spinal cord/brainstem
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M1 cells monkey experiment
monkey had LEDs on a screen, and whichever LED lit up it has to move it to that one while its contralateral hemisphere to the arm in use was recorded - firing rate of a particular neuron had a bell shaped curve depending on the direction of movement to be generated
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Multi electrode extracellular recording
ability to put many electrons in the brain at the same time - have been used in the motor cortex to record hundreds of neurons at the same time, allowed the discovery that the population vector of M1 cells predicts where the arm moves a very brief period of time after
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Robotic arm
Multi electrode extracellular recording can be used to record M1 cells and figure out where movement is being directed to control the movement of a robotic arm
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motor neuron pool
all the motor neurons that control a single muscle fibre
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Motor units
single motor neurons and all the muscle fibres that it innervates
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Motor units size
We do not need fine control in large muscles, but many smaller muscles do - however, larger muscles usually require more power, so the motor units are larger
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motor neuron cell bodies
for one muscle are distributed over multiple spinal segments, so the topography is not as distcete as touch neurons
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neuromuscular junction
synapse between neuron and muscle fiber
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Axons from motor neurons
have synaptic vesicles and calcium channels, but they release acetylcholine transmitters, resulting in excitation-contraction coupling
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clearing ACh
breaking down acetylcholine by acetylcholinesterase, which breaks down up to 5000 molecules of ACh a second - very important that contraction occurs only when action potentials are fired, and that they stop when firing stops
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Amyotropic lateral sclerosis
results in the death of lower and upper motor neurons, causing flaccid paralysis, areflecia, muscle atrophy, and can be fatal if it affects certain muscles
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Duchenne muscular dystrophy
x-linked recessive genetic mutation that causes death of skeletal muscle, the gene encodes for dystrophin, which is a muscle cytoskeletal protein
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Myasthenia gravis
autoimmune destruction of skeletal muscle ACh receptors, but alpha motor neurons and muscles are not damaged and it has normal life expectancy with treatment - one treatments is to reduce the activity of acetylcholeresterase, stopping the breakdown of ACh
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knee-jerk/stretch reflex
occurs when a muscle is stretched, and the reflex causes the muscle to contract back to counteract the stretch
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Stretch reflex pathway
muscle has sensory 1a afferent axons that opening mechanically gated ion channels to depolarize during stretch, 1a axon enters the dorsal horn and goes to the ventral horn, releasing glutamate onto the alpha motor neuron, causing it to release ACh onto the muscle to cause contraction, however, the antagonist muscle wants to be relaxed while this happens, so the 1a afferent also synapses onto an inhibitory interneuron, synapsing onto antagonist's alpha motor neuron.
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why does the stretch reflex occur
as you sit/stand, you tend to drift to one side, stretching muscles on the opposite side, so contraction of those could keep you upright, if you are walking, calf muscles become stretched, so contraction may help you spring back up, adding rhythm to walking
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autogenic inhibition reflex
when you voluntarily contract a reflex, the muscle contracts slowly to make sure it's not contracting too fast/jerky
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autogenic inhibition reflex pathway
When you begin contraction, 1b afferents in the golgi tendon detects
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synapsing onto antagonist's alpha motor neuron.
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autogenic inhibition reflex pathway
When you begin contraction, 1b afferents in the golgi tendon detects the increase in tension in the muscle, firing action potentials and synapsing onto an inhibitory interneuron that synapses onto the alpha neuron of the muscle to relax the muscle/lower the firing rate a little to lower the sharpness of contraction - also sends a branch to an excitatory interneuron which synapses onto the motor neuron of the antagonist, causing it to slow the motion as it contracts
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flexion-crossed extension reflex
When you step on something sharp/painful, we immediately pull up that leg, but we also push down on the other leg to support your weight - flexes the leg in pain and extends the other leg.
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flexion-crossed extension reflex pathway
Ad or C axons detect the stimulus, enter the dorsal horn and branch onto multiple excitatory interneurons, some decussating. They activate other interneurons which go to excite flexor muscles and relax extensor muscles on the pain side, and activate the extensor and inhibit the flexor on the non-pain side - all occurs before conscious awareness due to the slowness of Ad and C axons and since the reflex only occurs in the spinal cord
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Plasticity
capacity for continuous alteration of the neural pathways and synapses of the living brain and nervous system in response to experience or injury that involves the formation of new pathways and synapses and the elimination/modification of existing ones
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Aplysia
sea slug with gills to extract oxygen, and water exits the siphon. It has tactile sensors via tentacles at its head and two rinophores that are chemical sensors as well. It releases a dye when startled
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gill withdrawal reflex
occurs when a stimulus touches the siphon, causing the gill to withdraw to protect itself
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gill withdrawal reflex pathway
there are sensory neurons in the siphon skin and neurons release glutamate onto a motor neuron which releases ACh onto the gill muscles so that it withdraws
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aplasia habituation
transduction mechanism may fatigue, sensory neuron may release less glutamate onto the motor neuron, motor neuron may release less ACh onto the gill muscle, gill muscle fibers may fatigue
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aplasia sensitization
tail was shocked and the siphon was touched with the same force, they found the retraction of the gills was heightened
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sensitization pathway
tail skin has a sensory neuron which releases glutamate onto the modulatory/facilitatory interneuron, which releases serotonin onto an axo-axonic synapse. Serotonin binds to metabotorpoic serotonin receptors which activates adenylyl cyclase by a g-protein to syntheizes cAMP which activates protein kinase A which phosphorylates the potassium channel, causing them to not open as effectively, elongating the falling phase and causing more calcium entry
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extracellular electrical stimulation
stimulating microelectrode with negative charge causes negativity in the cerebrospinal fluid outside the axon, so the inside becomes more positive compared to the outside, causing a depolarization detected by the voltage gated sodium channels, that causes an action potential in both directions
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rat hippocampus extracellular electrical stimulation
used to stimulate two of the presynaptic pyramidal neuron axons, which both release glutamate onto postsynaptic pyramidal neurons, which are recorded through whole-cell recording - high frequency stimulation (tetnaus) to axon 1 causes an increase in the EPSP amplitude evoked by a subsequent single stimulus of axon 1, but no change to the EPSP evoked by axon 2 - this strengthened the synapse (LTP)
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Associativity
refers to the fact that during tetanus, if even one action potential was sent to axon 2, it's synapse was also strengthened
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Cooperativity
when you give paired action potentials to both for many minutes, and slowly both action potentials will strengthen their synapses - if this was only given alone, no strengthening would occur
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Pyramidal neuron dendrites
have little spines which are where the glutamatergic pre-synaptic neuron synapses are - they have normal AMPA receptors and NMDA receptors
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NMDA receptors
blocked by magnesium ions at resting potential - permeable to calcium and sodium, so when calcium enters the cell and depolarizes that spine, magnesium is repelled due to the positive inside of the cell, allowing calcium to enter the cell, but glutamate must be bound for it to open
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LTP initiation
when calcium enters the spine through the NMDA receptor
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LTP mechanism
When many action potentials are fired in the tetanus, there is a lot of glutamate in the area around the spine of axon 1, causing depolarization in this spine via the AMPA channels, but then allowing the NMDA receptor to let calcium in to cause LTP at axon 1
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associativity mechanism
there is glutamate at axon 2, and the axon is already depolarized, causing the NMDA receptor to open
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cooperativity mechanism
postsynaptic cell eventually becomes depolarized by the AMPA receptor, causing the NMDA channel to eventually open
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CAM kinase II
activated by calcium that enters through NMDA receptors - can phosphorylate the AMPA receptor to increase its conductance so more sodium is let in in subsequent action potentials, or can cause the insertion of new AMPA receptors in the membrane
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Fluorescene
an excitation light is used to excite electrons in the substance which absorb the energy of the excitation light, then falling to a lower energy level and losing little energy as heat which causes the surrounding molecules to vibrate, finally dropping to its resting state, giving off a light that is proportional to the drop in energy
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stokes shift
the drop of energy (the part given off by hear) - the light given off is a higher wavelength than the excitation light
359
calcium imaging
wavelength of light that comes back is the same, but the intensity of light varies based on the concentration of calcium
360
Fura-2
ultraviolet light is used as excitation, green is given off, varying the intensity of green light emitted based on the concentration of calcium
361
insertion of Fura-2
1. whole cell patch clamp pipette (diffuses in) 2. bulk electroproation (if a strong current is used, pores can be created to push the dye in) 3. Dextran-conjugate loading (injection into presynaptic axon terminals, transported through anterograde axonal transport) 4. viral transduction (virus DNA has the protein, cell produces indicator for days or weeks) 5. transgenic (genetically altered individuals who make the protein in some neurons)
362
declarative/nondeclarative memory
available - history, daily eposides - i know that... or not available to consciousness - motor skills, priming cues - i know how to...
363
retrograde and anterograde amnesia
loss of previously stored memories, inability to form new explicit memories
364
hippocampus
on the ventral surface of the temporal lobe - involved in the consolidation of new explicit long term memories and appears not to be involved in the storage of long term explicit memories or the consolidation of implicit memories
365
Henry Molaison
had severe epilepsy in the hippocampal area, eventually they removed the hippocampus and surrounding regions from both sides (bilateral hippocampectomy), which caused profound anterograde amnesia and temporally graded retrograde amnesia - older memories were kept intact and new implicit memories, could be aquired, but no working memory.
366
temporally graded retrograde amnesia
loss of memory of some events in the decade preceding surgery
367
individual sees/smells a rose for the first time
olfactory and visual neurons are strongly activated. They both cause weak EPSPs on the dendrites of the hippocampal neuron at A and B, so there must be cooperative LTP at these synapses, and then become stronger connections, so new action potentials will have larger effects
368
strong input is paired with
weak inputs back to the cortical neurons, allowing for associative LTP at synapses C and D, strengthening these synapses
369
how are long term memories formed
Over months/years, spontaneous action potentials are fired by the hippocampal neuron, causing action potentials in the cortical neurons. These cortical neurons have weak connections between them, causing weak EPSPs simultaneously at E and F, eventually causing associative LTP to strengthen these connections
370
how does life begin?
Fertilization of an egg occurs, which forms an embryo and divides to form pleuripotent embryonic stem cells, which give rise to ectoderm (brain, skin), mesoderm (muscle, bone, cartilage, blood), endoderm (lung, liver, gut) or germline (sperm, egg) cells
371
neural plate/groove
At day 18, there is a patch of the ectoderm called the neuroectoderm, which develops into the neural plate, which at day 20 becomes the neural groove, which becomes the neural tube, which forms the nervous system
372
mesoderm
develops into somites which become bone
373
notochord
becomes the vertebral column
374
floorplate
midline part of the neural tube - The upper part (neural crest cells) becomes the peripheral nervous system
375
development past day 20
As cells keep being born, the neural tube closes in the rostral and caudal direction - neural tube forms CNS, neural crest cells form PNS, and somites form skeleton and axial muscles
376
Spina Bifida
when the neural tube fails to close caudally. Exposed nerves may result in infection, affect bladder and bowel function, and cause paralysis
377
Spina Bifida risk factor
insufficient folate (B9) consumption during pregnancy, as it is needed for the production of DNA and RNA for mitosis
378
Spina Bifida Oculata
more mild form, where the nerves do not protrude through the skin and often has no symptoms
379
Anencephaly
when the neural tube fails to close rostrally, so much of the brain does not form and the baby does not live long. Again, folate is a risk factor as it is needed for DNA and RNA production for mitosis
380
Radial glia cells
move up and down, and when they move down they divide either symmetrically or asymmetrically (one daughter becomes a neuroblast and the other a radial glial)
381
migration
After the young neurons are born, they begin to migrate outward from the neural tube up the radial glial cells scaffold to what will be the cortex
382
X-lined Lissencephaly
caused by mutation of doublecortin (DCX) on the X-chromosome, affecting the migration of neurons, causing a smooth cortex (no sulci and gyri), causing issues eating, issues swallowing, seizures, and intallecutal impairment. In females, symptoms are not lissencephaly, but instead a disorder in the layers of the cortex (typically an outer and inner cortex)
383
axon growth
tip of the axon as it grows is a growth cone with finger-like filopoidia - growth cones grow about 0.5-2mm/day, similar to slow axonal transport
384
Chemoattractors/chemorepulsors
cues released by cells that the axon moves towards, or turns around to move away from
385
calcium imaging of a growth cone
calcium enters at the filopodia when chemoattractants are encountered, flowing into the lamelopodia of the growth cone - when a chemoattractant was placed in a dish, calcium was seen entering the filopodia, so calcium concentration regulates growth cone extension
386
Types of cues
long range (secreted by a cell, enters CSF and diffuses, causing a concentration gradient in the fluid) or short range (non-diffusible, are attached to a cell or the extracellular matrix, are only detected on contact with the growth cone)
387
mice nasal axon decussation
temporal retinal axons express EphB1 receptors on their growth cones, which bind to ephrin-B2 (contact repellent) on the membranes of glial cells in the optic chiasm, repelling them - likely a diffusable chemoattractant that makes all the axons go the optic chiasm, but only the temporal are repelled
388
ST tract decussation in frogs
floorplate secretes netrin (chemoattractor), creating a concentration gradient which is largest in the midline, and slit (chemorepellent), so as the axon grows towards the midline, slit binds to the Robo1 and Robo2 receptors on the growth cone, but before growing to the midline less Robo is expressed and the axon is insensitive to slit. However, when the axon crosses the midline, Robo is produced and slit binds, repelling the axon from the midline.
389
Robo receptors
originally discovered in fruit flies, which have the same slit ligand. Similar Robo receptors were discovered in many other species
390
Robo3
Robo in mammals - does not bind to slit, but plays an important role in attracting the axon to the midline for decussation, and after decussation Robo3 expression is reduces
391
infraorbital nerve decussation in rats and mutated Robo3
infraorbital nerve enters the brainstem in the pons, forming synapses in the principal trigeminal nucleus. Decussation occurs, then ascending to the ventral posterior medial thalamic nucleus, then going to layer 4 of the cortex. When the Robo3 receptor was mutated, abnormal ipselateral and normal contrlateral projection was seen instead of only normal contrlateral projections
392
Robo3 and the LSO
When Robo3 was mutated, projections were sent to the ipselateral LSO and MNTB
393
vestibular nucleus and Robo3
vestibular nucleus sends axons to the abducens nucleus through decussation, which decussates again eventually going to the eye. The second decussation does not occur in Robo3 mutant mice, causing eye movement problems, can occur in humans, causing issues with eye movements
394
LCST and Robo3
Robo3 mutations cause no decussation for the LCST in the medulla. When an individual was asked to do a motor task, movement of the right hand activated only the right motor cortex due to a Robo3 mutation - opposite of what it should be
395
Trophic factors
produced by a target tissue to support presynaptic neurons and promote dendritic and axonal elaboration once the target is reached (Nerve growth factor, neurotrophins, brain-derived neurotrophic factor)
396
NGF
nourishes free nerve endings in the skin (Ad and C axons)
397
NT-4 and NT-5
Nourish hair cells
398
NT-3
released by muscle spindles onto the 1a axon
399
Trk receptors
tyrosine kinase receptors, set up a signalling cascade in the axons
400
P75
binds all of the NT factors
401
Limits to trophic factors
presynaptic axons compete for space on the tissue, and survival, eventually one axon wins and the others withdraw - a single neuromuscular junction in the neonatal mouse over sequential days was imaged, and it could be seen that one axon eventually withdrew
402
refining the LSO/MNTB to tell two sounds apart
LSO and its inputs must be tonotopically organized, and the excitatory and inhibitory inputs are aligned in register/frequency - after synaptic connections are formed, they need to be pruned so the pathways are efficient
403
Hebbian plasticity
neurons that fire together wire together - when an axon of cell A is near enough to excite cell B persistently/repeatedly, some metabolic change takes place in one or both of them increasing A
404
Hebbian plasticity
neurons that fire together wire together - when an axon of cell A is near enough to excite cell B persistently/repeatedly, some metabolic change takes place in one or both of them increasing A's efficiency and the firing of B is increased
405
circuitry refinement
Those synapses which are not strengthened are weakened and do not survive, the ones that do survive sprout collaterals. So, neural activity is required to refine neural circuitry
406
amacrine cells
look like horizontal cells and make lateral connections
407
Starburst amacrine cells
cause spontaneous retinal waves in early postnatal lids by releasing acetylcholine that promote eye-specific segregation in the LGN and cortex before the eyes even open - it is spontaneous and not dependent on visual input
408
function of starburst amacrine cells
They are hypothesized to sort inputs from each retina onto different cells through Hebbian mechanisms so that in the thalamus and in layer 4, the two eyes inputs are segregated - first step in activity dependent circuitry refinement
409
Radioactive amino acids experiment
injected into the eye, and they could be seen isolated in different layers in the LGN, but in a zebra-like pattern in layer 4, proof that what comes from one eye is isolated to specific neurons
410
Monocularly deprived animals experiment layer 4
If done in the right time period, the Zebra pattern in layer 4 turns into an area dominated by the open eye - in normal animals, axon arbours in layer 4 are seen, but in deprived eyes, the arbour looks more wispy and synapses on less neurons
411
Amblyopia
impaired vision that is not caused by problems to the eye itself
412
Monocularly deprived animals experiment superficial cortex
In the early monocular deprived animal, all the axons respond only to the always stimulated eye, in the late monocular deprived animal, the normal bell shaped curve was noticed, even if the eye was kept closed for longer - in the critical period, even if only deprived for 6 days, neurons only responded to one eye.
413
strabismic
one eye looks in a different direction than the other
414
strabismic animals experiment
found that neurons were split mostly between the two eyes, very few responding to both eyes (each eye had different visual field)
415
orientation tuning experiment
simple cells on the left and right eye have exactly the same tuning curves, just in separate eyes. Early, curves are not well defined, becoming sharper and eventually aligning. If an eye is closed during the critical period, there is no alignment, even when opened again. If the eye is closed as an adult, alignment still occurs and no effect is seen.
416
Aequorea victoria
jellyfish that uses GFP to fluoresce
417
Brainbow
Transgenic mice and GFP/related proteins were used to make the mice produce the fluorescent proteins of different colours, so neurons of different colours in the mice could be created
PNB 2XB3 - NEURO
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Decks in class (5)
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