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Question 1

Calculate an equilibrium potential using the Nernst equation (Cellular excitability 1-3)

Answer 1

Eion = 2.303 RT/zF log [ion]o/[ion]i

Question 2

Recognise the electrical and chemical forces that produce the resting membrane potential (Cellular excitability 1-3)

Answer 2

-K+ that leaks from the inside of the cell to the outside via leak K+ channels and generates a negative charge in the inside of the membrane vs the outside. At rest, the membrane is impermeable to Na+, as all of the Na+ channels are closed.
-Neuronal membrane separates electrically charged ions
-Ions can cross membrane by way of protein channels and pumps, highly selective for specific ions
-Movement of any ion through its channel depends on the concentration gradient and difference in electrical potential across the membrane

Question 3

Explain the importance of the Na/K ATPase pump (Cellular excitability 1-3)

Answer 3

maintains the gradient of a higher concentration of sodium extracellularly and a higher level of potassium intracellularly, maintains a large K+ concentration gradient across the neuronal membrane

Question 4

Calculate a resting membrane potential using the Goldman equation (Cellular excitability 1-3)

Answer 4

Vm = 61.54mV log (Pk [K+]o + PNa [Na+]o) / (Pl [K+]i + PNa [Na+]i)
-At rest, the neuronal membrane is very permeable to K+ due to open K+ channels
-Increasing extracellular K+ causes membrane potential to depolarise
-Resting membrane potential approaches Ek+

Question 5

Describe which membrane currents and ion channels are associated with the different phases of an action potential (Cellular excitability 1-3)

Answer 5

-AP is a rapid change in membrane potential from negative to positive
-AP often triggered by Na+ permeability increase
-Past threshold, voltage gated Na+ ion channels open
-Past 0mv, repolarisation, Na+ channels close and K+ channels open
-Hyperpolarization, K+ channels remain open after potential reaches resting level

Question 6

List the major features of an action potential: its initiation, generation, conduction, propagation and refractory nature (Cellular excitability 1-3)

Answer 6

Initiation
-action potential is initiated by a depolarizing stimulus that causes the membrane potential to become less negative than the resting potential
Generation
-Once the membrane potential reaches a certain threshold, voltage-gated ion channels in the membrane open, allowing an influx of positively charged ions into the cell. This depolarizes the membrane further and triggers the rapid rise in voltage
Conduction
-The depolarization of the membrane triggers neighbouring voltage-gated ion channels to open, causing a self-propagating wave of depolarization to spread along the length of the cell membrane
Propagation
-The AP propagates down the axon of the neuron, which is covered in myelin sheath, acting as an insulator, allowing the action potential to jump from one node of Ranvier to the next. This process speeds up the propagation of the action potential along the axon
Refractory nature
-After AP is generated, the membrane potential undergoes a period of hyperpolarization due to the efflux of positively charged ions. Membrane is temporarily resistant to further depolarization. Ensuring that AP propagates in one direction and prevents it from being triggered again too soon.

Question 7

Describe the important features of graded membrane potentials. (Cellular excitability 1-3)

Answer 7

-GP are proportional in amplitude to the size of the input stimulus.
-GP may be depolarizing or hyperpolarizing.
-GP travel passively, uniformly in all directions. don’t require voltage-gated channels.
-GP can summate, temporally and spatially

Question 8

Describe the main steps of chemical neurotransmission: making vesicles, filling them, and releasing them; how neurotransmitters act on postsynaptic receptors and what happens downstream in the postsynaptic cell; neurotransmitter inactivation; and how these steps are regulated (Synapses and Neurotransmitters 1-3)

Answer 8

-Synaptic vesicles created in the golgi apparatus
-Neurotransmitters packaged into vesicles
-Vesicle placed at presynaptic terminal
-AP arrives, voltage gated Ca2+ channels open
-Ca2+ influx causes vesicles to fuse to the membrane via SNAREs
-Neurotransmitters released into the synaptic cleft
-Vesicle taken up again by endocytosis
-Neurotransmitters diffuse across the synaptic cleft, binding to receptors on the postsynaptic cell
-Ligand-gated ion channels = directly depolarise or hyperpolarize the postsynaptic cell
-Neurotransmitters removed from the synaptic cleft (do not enter postsynaptic cell)
-Process is regulated by action potentials

Question 9

Identify the major excitatory, inhibitory and modulatory neurotransmitters, their roles, their mode of action, and how they are synthesised and degraded/removed. (Synapses and Neurotransmitters 1-3)

Answer 9

Glutamate
-Amino acid
-Glutamate is formed directly from glutamine
-Released by calcium dependent exocytosis
-Produces EPSPs
-AMPA & NMDA receptors
-Selective uptake into presyn terminals & glia
-Important to memory, cognition, and mood regulation
-CNS
-postsynaptic glutamate receptors
GABA
-Amino acid
-Synthesised from glutamate by glutamic acid decarboxylase
-Released in a Ca2+ dependent manner upon depolarization of the presynaptic membrane
-Produces IPSPs via GABAA and GABAB receptors
-Selective uptake into presynaptic terminals & glia
-Reduce neuronal excitability by inhibiting nerve transmission.
-CNS
-hippocampus, thalamus, basal ganglia, hypothalamus, and brainstem
Acetylcholine
-Synthesised in nerve terminals from acetyl coenzyme A (acetyl CoA, which is synthesised from glucose) and choline, in a reaction catalysed by choline acetyltransferase (CAT)
-Release of acetylcholine occurs when an action potential is relayed and reaches the axon terminus in which depolarization causes voltage-gated calcium channels to open and conduct an influx of calcium, which will allow the vesicles containing acetylcholine for release into the synaptic cleft
-Acetylcholine receptors (AChRs), like many other ligand-activated neurotransmitter receptors, consist of two major subtypes: the metabotropic muscarinic receptors and the ionotropic nicotinic receptors
-ACh is removed from the synaptic cleft by acetylcholinesterase (AChE)
-Regulating cardiac contractions and blood pressure, intestinal peristalsis, glandular secretion, etc. Typically, acetylcholine is an excitatory mediator
-Basal forebrain and the mesopontine tegmental area

Question 10

Relate the process of development to the nervous system structure (Nervous system structure through development)

Answer 10

Neural Induction:
-Involves the differentiation of the neural plate from the ectoderm of the embryo.
-Regulated by various signaling molecules
Neural Tube Formation (neurulation):
-The neural plate folds inward to form the neural tube.
-Involves complex cellular movements and interactions.
-The neural tube gives rise to the CNS
-The anterior portion of the neural tube develops into the brain
-The posterior portion forms the spinal cord.
Neurogenesis:
-The generation of neurons from neural stem cells
-Neural stem cells undergo cell division and produce neuroblasts.
-These neuroblasts then differentiate into specific types of neurons through a process called neuronal specification
-Occurs in a temporally and spatially controlled manner
Axon Guidance and Synaptogenesis:
-As neurons differentiate, they extend axons and form connections with other neurons to establish the neural circuitry
-Once axons reach their target regions, synaptogenesis occurs
-Involving the formation of synapses between neurons
Neural Plasticity:
Refers to the ability of the nervous system to change and adapt through growth and reorganization in response to internal and external stimuli

Question 11

Identify the important structures of the nervous system (Nervous system structure through development)

Answer 11

Forebrain - lateral ventricles and third ventricles, cerebral cortex, thalamus, hypothalamus, basal telencephalon, corpus callosum, cortical white matter, internal capsule
Midbrain - Tegmentum, Cerebral aqueduct, tectum
Hindbrain - fourth ventricle, cerebellum, pons
The central nervous system is made up of the brain and spinal cord. The peripheral nervous system is made up of nerves that branch off from the spinal cord and extend to all parts of the body
The peripheral nervous system refers to parts of the nervous system outside the brain and spinal cord. It includes the cranial nerves, spinal nerves and their roots and branches, peripheral nerves, and neuromuscular junctions

Question 12

Describe the cytoarchitectural structure of the neocortex and how this relates to the construction of Brodmann’s cytoarchitectural map. (The Brain)

Answer 12

The neocortex has 6 layers, the exact structure differs between regions of the neocortex.
Split into lobes and then defined by functional areas
-Temporal lobe
-Primary auditory cortex
-Frontal to parietal lobe distinguished by the central sulcus
-Frontal cortex - PFC - involved in higher ordering processing
-Parietal lobe - somatosensory cortex (touch signals enter here)
-Occipital lobe - posterior (visual lobe)
Brodmann mapped all of the brain, the neocortex to each area of the brain, (using lesions or direct stimulation)
Can map using non invasive (PET, fMRI and EEG)

Question 13

List the major features of cellular models of learning and memory such as long-term potentiation. (Memory)

Answer 13

-Long-term potentiation (LTP) is a process involving persistent strengthening of synapses that leads to a long-lasting increase in signal transmission between neurons. It is an important process in the context of synaptic plasticity. LTP recording is widely recognized as a cellular model for the study of memory
-Long-term potentiation has three essential properties: input specificity, cooperativity, and associativity
-Long-term depression (LTD) is the opposite of LTP, and is characterised by a decrease in postsynaptic strength. This happens by dephosphorylation of AMPA receptors and the facilitation of their movement away from the synaptic junction

Question 14

Define:
Receptor potential (Principles of Sensory Systems)

Answer 14

type of graded potential
the transmembrane potential difference produced by activation of a sensory receptor

Question 15

Describe the structure and principal cell types of the retina. (The Visual System 1 - the Eye and Retina)

Answer 15

Laminar organisation of the retina
Light focussed on the retina must be converted into neural activity
Light must pass through ganglion and bipolar cells before reaching photoreceptors
Ganglion cells - output from retina
Amacrine cells - modulate information transfer between GC’s and BC’s
Bipolar cells - connect photoreceptors to ganglion cells
Horizontal cells - modulate information transfer between photoreceptors and BC’s
Photoreceptors - sensory transducers, rods and cones

Question 16

Describe the intracellular signalling process involved in phototransduction (The Visual System 2 - Phototransduction)

Answer 16

Rod photopigment - rhodopsin
Cone photopigment - S/M/L opsins
Retinal photopigment - melanopsin
Photoreceptors are hyperpolarized by light
Rhodopsin activated by light, stimulates the G-protein, transduction, to become transduction GPT
α subunit activates the enzyme, phosphodiesterase (PDE)
PDE reduces cGMP levels, closing Na+ channels
Signal amplification occurs as this is an enzyme cascade

Question 17

Describe the transduction mechanism in olfactory receptor cells (The Visual System 2 - Phototransduction)

Answer 17

Begins with odorant molecules binding to olfactory receptors, which are G protein-coupled receptors located on the cilia of olfactory receptor cells in the olfactory epithelium of the nasal cavity.
Then activates a G-protein called Golf, which in turn activates an enzyme called adenylate cyclase. Adenylate cyclase converts ATP into cyclic AMP (cAMP), which serves as a second messenger and opens cyclic nucleotide-gated ion channels in the cilia membrane. This results in the influx of positively charged sodium (Na+) and calcium (Ca2+) ions, which depolarizes the olfactory receptor cell and generates an action potential.
The depolarization of the olfactory receptor cell triggers the release of neurotransmitters, such as glutamate and GABA, which then activate nearby mitral cells in the olfactory bulb of the brain. The olfactory bulb processes the information from the olfactory receptor cells and sends the resulting neural signals to the olfactory cortex, where they are interpreted as specific odour perceptions.
The olfactory receptor cells have the ability to detect a wide range of odorants due to the presence of a large family of olfactory receptors, which are capable of binding to different odorant molecules with varying degrees of specificity.

Question 18

Discuss how receptor potentials trigger action potentials in the primary afferent neurons of the gustatory and olfactory systems (The Chemical Senses)

Answer 18

In both the gustatory and olfactory systems, receptor potentials are generated in response to specific stimuli and serve to trigger action potentials in the primary afferent neurons, which convey the sensory information to the brain for further processing and perception of taste and smell

Question 19

Recall the organisation of cells within the glomerulus (The Chemical Senses)

Answer 19

Each glomerulus of the olfactory bulb receives input from only one type of olfactory receptor
The glomerulus is a spherical structure in the olfactory bulb of the brain that serves as the initial site of processing for olfactory sensory information
There is convergence on second order neurons, second order neurons carry information from glomeruli to various regions of the brain

Question 20

Note the major anatomical structures and cells of the peripheral vestibular system (The Vestibular System)

Answer 20

Vestibular organs
-Two vestibular organs in each ear, the utricle (left/right/backwards/forwards) and saccule (up/down)
-The three semicircular canals, which detect angular acceleration & head rotation, each has an ampulla
Hair cells AKA stereocilia
-Found in sensory patch called macula within utricle, a line through it called the striola, setting polarity for hair cells, activated by the gelatinous otolithic membrane
-When the head moves, the fluid in the vestibular organs pushes on the cupula or otolithic membrane, causing the stereocilia to bend and depolarizing the hair cells.
-Type I hair cells attach to afferent dendrite that has a calyx
Vestibular nerve fibres
-The primary afferent neurons that carry information from the vestibular organs to the brainstem and other parts of the central nervous system
-There are two types of vestibular nerve fibres: type I and type II.
-Type I fibres synapse with hair cells in the utricle and saccule,
-Type II fibres synapse with hair cells in the semicircular canals.
Ampulla
-Each semicircular canal has an ampulla containing hair cells that are embedded in a gelatinous structure called the cupula.
-When the head rotates, the fluid in the semicircular canal moves and causes the cupula to bend, which in turn causes the hair cells to be activated and generate electrical signals that are transmitted to the brain

Question 21

Describe the mechanisms involved in the detection of linear and rotational acceleration. (The Vestibular System)

Answer 21

Linear acceleration
-The utricle and saccule each contain a patch of hair cells covered by a gelatinous layer containing tiny crystals called otoliths.
-When the head moves in a linear direction, the otoliths move in response to the force of gravity, causing the gelatinous layer to bend the hair cells beneath it. This bending activates the mechanotransduction channels in the hair cells, allowing the entry of ions, leading to depolarization, and the release of neurotransmitters at the synapse with the vestibular nerve fibres.
-The information from the utricle and saccule is then processed by the brain to determine the direction and magnitude of linear acceleration.
Rotational acceleration
-The semicircular canals are filled with fluid and oriented in three different planes, each corresponding to a different axis of rotation.
-Each semicircular canal contains a gelatinous structure called the cupula, which contains hair cells.
-When the head rotates, the fluid in the semicircular canals lags behind, causing the cupula to bend and stimulate the hair cells within. The bending of the hair cells activates the mechanotransduction channels, leading to depolarization, and the release of neurotransmitters at the synapse with the vestibular nerve fibres.
-The information from the semicircular canals is then integrated by the brain to determine the direction and magnitude of rotational acceleration.

Question 22

Recognise the main CNS structures involved in vestibular processing (The Vestibular System)

Answer 22

Vestibular nuclei
-Located in the brainstem and receives input from the vestibular organs. They are responsible for integrating vestibular information with other sensory inputs, such as visual and somatosensory inputs, to maintain postural stability and coordinate movements.
Cerebellum
-Receives input from the vestibular nuclei and is involved in the control of balance and coordination of movements. It plays a crucial role in the adaptation of vestibular reflexes to changes in the environment.
Thalamus
-Receives input from the vestibular nuclei and projects to the cerebral cortex. It is involved in the processing of vestibular information related to spatial orientation and perception.
Cerebral cortex
-Receives input from the thalamus and is involved in the conscious perception of vestibular sensations, such as dizziness and vertigo. It also plays a role in the integration of vestibular information with other sensory inputs to maintain spatial awareness and coordinate movements.

Question 23

Recall the different types of sensory receptor and their function (Somatic Sensory System)

Answer 23

Two major input components of ‘body sense’ in the brain
-Mechanical stimuli (touch, vibration, pressure, etc)
-Painful stimuli and temperature
Golgi tendon organs
-tension or force generated by a muscle during muscle contraction
Muscle spindles
-detect changes in the length of the muscle fibres
Hair follicles
-modality varied according to type
Encapsulated nerve endings
-Meissner (or tactile) corpuscle
—–Detect light touch and texture
—–Rapidly adapting
-Pacinian (or lamellated) corpuscle
—–Deep pressure and vibration
—–Rapidly adapting
-Ruffini corpuscle
—–Heavy touch and pressure
—–Slowly adapting
Unencapsulated nerve endings
-Merkel (or tactile) disks
—–Light touch and texture, edges and shapes
—–Slowly adapting
-Free nerve endings
—–pain , heat, cold
Rapidly adapting or phasic receptors give information about changes in the stimulus
Slowly adapting or tonic receptors give information about persistence of stimulus
Primary afferent axon subtypes, classified according to conduction velocity
Faster = larger diameter
-‘A, B, C’ - coming from the skin
-‘I, II, III, IV,’ - coming from the muscles
Pain fibres slower than proprioceptors

Question 24

Note the organisation of the dorsal column – medial lemniscal projection. (Somatic Sensory System)

Answer 24

Cell bodies of different classes of sensory neuron grouped into the dorsal root ganglion and their projections organised into different layers of the dorsal horn
The dorsal column-medial lemniscal (DCML) pathway is an ascending somatosensory pathway
The medial lemniscal tracts carry mechanoreceptive and proprioceptive signals to the thalamus
The spinothalamic tract carries pain and temperature signals to the thalamus

Question 25

Recall the organisation of the projection to the thalamus and cerebral cortex (Somatic Sensory System)

Answer 25

Typically sensory information travels through three neurons to reach higher centres:
-First order neurons - detect the stimulus and transmit to spinal cord
-Second order neurons - relay the signal to the thalamus, ‘gateway’ to the cortex
-Third order neurons - carry the signal from the thalamus to the cortex
Axons of the medial lemniscal pathway are topologically organised
-First order axons from upper body follow lateral pathway and synapse on second order neurons in the cuneate nucleus
-First order axons from the lower body follow the medial pathway and synapse on neurons in the gracile nucleus
—–Together the cuneate and gracile are known as the dorsal column nuclei
-Second order axons cross the midline and ascend in the medial lemniscus
-Therefore their topology is reversed relative to the midline so that lower body axons are more lateral on reaching the thalamus
-Third order axons again reverse the topology so that lower body axons synapse on more medial cortical neurons whereas upper body axons map to the lateral cortex
The result of this topological projection is a map of the body in the cortex
Each sensory ganglion innervates a specific region of skin called a dermatome
The dermis of each region is derived from a specific embryonic structure called the somite
In the embryo, each DRG is associated with with a specific somite
This topological organisation is preserved in the spinal cord and the somatosensory projections
Each sensory neuron has a receptive field
Size of receptive field can be measured by assessing the ability to discriminate two sharp points set apart at different distances, if the subject feels two pin points then then the distance between the points is larger than the receptive field
Where receptive fields are large, discrimination is low
Where receptive fields are small, discrimination is high
Sensory modality also represented in the cortex
Somatotopic map is preserved in the coronal plane in the postcentral gyrus
Throughout the postcentral gyrus, different sensory modalities are localised along the sagittal axis
Brodmann areas refer to a system of numbering regions of the cerebral cortex based on differences in their cellular organisation and structure

Question 26

Summary (Somatic Sensory System)

Answer 26

The components of the somatosensory system process information conveyed by mechanical stimuli that impinge upon the body surface or that are generated within the body itself (proprioception)
This sensory information is relayed via first-, second- and third-order neurons from the receptors to the somatosensory cortex via the medial lemniscal system and the thalamus.
First-order neurons are located in the dorsal root ganglia, second-order neurons in the dorsal column nuclei, and third-order are found in the thalamus
The topology of the axons in these projections is preserved such that a topographic map of the receptors is created in the somatosensory cortex.
The area of cortex dedicated to each area of the body is proportional to the density of innervation in that area (and hence its behavioural significance) not to the physical size of the area
The modality of innervation is also represented in the cortex, functionally similar information projecting to the same cortical domain.
The cortex is highly plastic and can adapt to changes in its inputs.

Question 27

Recall afferent fibres associated with the transmission of different types of pain. (Pain)

Answer 27

Afferents with free nerve endings : nociceptors?
Lightly myelinated Aδ fibres, fast (slower than proprioceptors)
-Mechano-sensitive
-Mechano Thermal-sensitive
Unmyelinated C fibres, slow
-Polymodal : mechanical, thermal, and chemical
Two categories of pain mediated by different fibre types
-Fast ‘first’ pain, sharp and immediate
-Can be mimicked by direct stimulation of Aδ fibre nociceptors
-Slow ‘second’ pain, delayed, diffused, longer lasting
-Can be mimicked by stimulation of C fibre nociceptors
Thus there are a distinct set of Aδ and C fibres, nociceptors, specifically associated with pain detection

Question 28

Identify the major descending motor pathways. (Motor Control and Diseases 1)

Answer 28

The brain exerts control over spinal motor units via specific descending pathways
Corticospinal tract: Primary motor cortex of the brain to the spinal cord. Responsible for controlling voluntary movement of the body, particularly fine and skilled movements of the limbs. Divided into two parts: the lateral corticospinal tract, controls voluntary movement of limbs on opposite side of the body, and the ventral corticospinal tract, controls voluntary movement of the trunk on both sides of body
CST is one of the lateral pathways
Extrapyramidal tract: Originates in the basal ganglia and descends through the brainstem to the spinal cord. Responsible for controlling involuntary movement of the body (posture and balance) and helps to regulate voluntary movement. It is further divided into several subpathways
Ventromedial pathways control posture, project mainly ipsilaterally and medially
Vestibulospinal tract - head balance and turning
Tectospinal tract - orienting response
Reticulospinal tracts - control antigravity reflexes
90% of cortex is a six-layered structure
-Main inputs to the cortex are to stellate cells in layer IV
-Main outputs are from layers III, V, and VI
-Axons of corticospinal tract derive from large pyramidal cells in layer V

Question 29

Be aware of the direct and indirect pathways of the ‘motor loop’ and how these are affected by the reduction in dopamine in PD (Motor Control and Diseases 2)

Answer 29

Basal ganglia - the ‘motor loop’
-Motor cortex connects to the basal ganglia, feedback to the premotor area to control the initiation of movement
-Two pathways, direct and indirect
—–Direct pathway: Facilitates movement by disinhibiting the thalamus, while the indirect pathway inhibits movement by inhibiting the thalamus, involves the striatum and the globus pallidus internus
—–Indirect pathway, involved in inhibiting movement, substantia nigra has a complex role and acts via the striatum to maintain the balance between inhibition and activation of the VLo, the SN is balancing or ‘turning’ the activation of the VLo
Degeneration of neurons in different parts of this circuit leads to parkinson’s or huntington’s disease
Reduced dopaminergic input from substantia nigra to striatum leads to:
-Increased activity of the indirect pathway
-Decreased activity of the direct pathway
This means less inhibition of the GPi and so its inhibitory activity is increased
Leading to decreased activity of the VLo and so less motor cortex activation
L-DOPA reverses this effect only as long as some DA-ergic neurons survive