Neurology: Physiology - Nerve function

Question 1

What are the large molecule neurotransmitters? Give examples

Answer 1

Neuropeptides e.g. substance P, enkephalin, vasopressin
Usually co-localised with small molecule neurotransmitters

Question 2

Three types of synapses and their distribution in the cerebral cortex vs spinal cord

Answer 2

1. Axo-dendritic: 98% of synapses in cerebral cortex, 80% in spinal cord
2. Axo-somatic: 2% of synapses in cerebral cortex, 20% in spinal cord

Question 3

How many synaptic endings does each neuron have? How many neurons are in the CNS and therefore how many synapses are there?

Answer 3

> 2000 synaptic endings to each neuron
10^11 neurons in the CNS
2x10^14 synapses

Question 4

What are three different kinds of synaptic vesicles and what neurotransmitters does each contain?

Answer 4

1. Small, clear vesicles: ACh, glycine, GABA, glutamate
2. Small, dense-cored vesicles: catecholamines
3. Large, dense-cored vesicles: neuropeptides

Question 5

How wide is the synaptic cleft?

Answer 5

20-40nm

Question 6

What are neurexins?

Answer 6

Cell adhesion proteins on presynaptic and postsynaptic membranes which bind to mediate synaptic protein organisation

Question 7

What are EPSPs and IPSPs?

Answer 7

Excitatory and inhibitory postsynaptic potentials

Single stimulus to a nerve does not produced a propagated action potential in the postsynaptic neuron, but does produce either transient depolarisation (EPSP) or hyperpolarisation (IPSP), which accumulates when it is produced across multiple synaptic knobs

Question 8

Where do slow EPSPs/IPSPs occur and what is the duration of their latency period and their duration of action?

Answer 8

In autonomic ganglia, cardiac and smooth muscle, and cortical neurons
Latency of 100-500ms, last several seconds in duration

Question 9

Describe the process of an EPSP

Answer 9

Excitatory neurotransmitter binds receptors on postsynaptic neuron membrane and induces opening of Na+/Ca2+ channels
Na+/Ca2+ influx produces small EPSP (but not enough current to depolarise whole membrane)

Question 10

What is the duration of fast EPSP/IPSP latency and the total duration of action?

Answer 10

Latency 0.5ms
Peak action at 11.5ms then declines exponentially afterwards

Question 11

Describe spatial vs temporal summation

Answer 11

Spatial summation: activity of one terminal combines with activity of another to approach firing threshold
Temporal summation: repeated afferent stimuli cause new EPSPs before previous EPSPs decay to approach firing threshold

Question 12

What is EPSP proportional to?

Answer 12

Strength of afferent stimulus

Question 13

What are the two EPSP-generating neurotransmitters?

Answer 13

1. Glutamate
2. ACh

Question 14

What are three mechanisms by which IPSPs may be produced?

Answer 14

1. K+ channel opening and efflux
2. Cl- channel opening and influx
3. Na+/Ca2+ channel closure

Question 15

What is the IPSP-generating neurotransmitter?

Answer 15

GABA

Question 16

How does generation of action potential in a postsynaptic neuron occur?

Answer 16

There is a constant interplay of excitatory and inhibitory activity on postsynaptic neuron such that membrane potential is fluctuating
When threshold (10-15mV of depolarisation) is reached, a propagated spike results

Question 17

What is the initial segment of a motor neuron? Where is it located and what is its role?

Answer 17

In motor neurons, the portion of the cell with the lowest threshold for production of full action potential is called the “initial segment”, and is the portion of the axon at and just beyond the axon hillock

Fires first and produces a discharge which propagates in two directions (down axon and back into soma to “reset” membrane)

Question 18

What are the two types of inhibition?

Answer 18

Presynaptic
Postsynaptic

Question 19

What are the three methods of presynaptic inhibition?

Answer 19

Mediated at axo-axonal synapses via:
1. Increased Cl- influx (in turn reduced Ca2+ influx and therefore amount of neurotransmitter released)
2. Voltage-gated K+ channel opening (resulting in K+ efflux and reduced Ca2+ influx -> reduced neurotransmitter release)
3. Direct inhibition of transmitter release independent of Ca2+

Question 20

What are the two methods of postsynaptic inhibition?

Answer 20

1. Direct due to IPSP
2. Indirect due to influence of previous discharges of postsynaptic neuron (e.g. refractory period, after-hyperpolarisation)

Question 21

How does GABA produce presynaptic inhibition?

Answer 21

GABA(A) via Cl- influx
GABA(B) via K+ efflux

Question 22

When does presynaptic facilitation occur? Give an example

Answer 22

When Ca2+ channel opening and therefore action potential duration is prolonged
E.g. 5HT released at axo-axonal synapse causes increased cAMP -> phosphorylation and closure of K+ channels -> slowed repolarisation, prolonged action potential duration

Question 23

What are Renshaw cells?

Answer 23

Inhibitory interneurons in the spinal cord that provide negative feedback to motor neurons (via inhibitory neurotransmitter glycine), as they are stimulated by a collateral off the axon of the motor neuron, and their Renshaw cell terminals are on the soma of the cell

Question 24

What is summation?

Answer 24

Combined effect of multiple presynaptic neurons acting on a postsynaptic neuron

Question 25

What is occlusion?

Answer 25

The observation that the observed postsynaptic response from multiple presynaptic fibre signals is not as great as the expected response
Occurs when presynaptic fibres share postsynaptic neurons

Question 26

Describe the sequence of events at the neuromuscular junction

Answer 26

1. Motor neuron action potential
2. Ca2+ enters axon terminal via voltage-gated Ca2+ channels
3. Small, clear vesicles partially fuse to cell membrane and release ACh
4. ACh binds to ACh-receptors (ligand-gated Na+ channels) in motor end-plate, causing Na+ influx and depolarising (“endplate potential”)
5. Voltage-gated Na+ channels initiate and propagate the action potential
6. Muscle contraction occurs through excitation-contraction coupling
7. Acetylcholinesterase in motor end-plate degrades ACh

Question 27

What is the difference between skeletal and smooth muscle in terms of arrangement of axons?

Answer 27

There is not a single axon but rather a chain of “beaded” varicosities down the length of the neuron (each filled with vesicles) in an arrangement called synapse en passant

Question 28

What is denervation hypersensitivity?

Answer 28

Occurs when muscle is denervated, and it gradually becomes more sensitive to ACh

Question 29

How do axons degenerate when damaged?

Answer 29

Degenerate distal to site of injury (Wallerian degeneration), but also proximal to the site of injury up to the stump of the nearest collateral (retrograde degeneration)
Retrograde reaction also occurs in soma with chromatolysis (rough ER fragmentation)