Neurotransmission

Question 1

Differentiate between autonomic and sensory-somatic nervous system.

Answer 1

1. Somatosensory system:
   – Neurons that receive sensory information and control movement of skeletal muscle.
2. Autonomic system:
   – Neurons that receive sensory information and regulate movement of smooth muscle and cardiac muscle as well as glandular secretion.
   – Sympathetic and parasympathetic control.

Question 2

Differentiate between sensory and motor neurons

Answer 2

1. Sensory: Afferent neurons that send information to the CNS about the internal and external environment.
2. Motor: efferent (away) neurons control the activity of the body by controlling muscle and gland functions (contraction, relaxation, secretion).

Question 3

Define what a neurotransmitter is.

Answer 3

• Chemical messengers released at the end of a nerve fibre and diffuses across the synapse and affects the transfer of the impulse to another nerve fibre, a muscle fibre, or some other structure.
• E.g dopaminergic, glutamatergic, cholinergic.
• They are either excitatory, inhibitory or other (serotonin, dopamine, Nora.).
• Each NT has specific receptors.

Question 4

Discuss NT synthesis.

Answer 4

• Synthesised locally within the axon terminal from precursors.
• These precursors are either taken up by selective transporters on the membrane of the terminal or readily available by-products of cellular processes that take place within the neuron itself.
• enzymes needed for this reaction are produced in the cell body & transported to the terminal by slow axonal transport.

Question 5

What are the types of NT receptors?

Answer 5

1. Ionotropic receptors:
   – Ligand-gated ion channels
   – NT binding increases permeability to ions
   – Fast synaptic transmission
2. Metabotropic receptors:
   – G-protein coupled receptors (GPCR)
   – Slower synaptic transmission
   - NT binding activates G-protein that either directly modifies function of ion channels or triggers production of a second messenger (e.g. cAMP)
   - Mediates short-term as well as long-term effects.

Question 6

Differentiate between depolarisation (excitation) and hyper-polarisation (inhibition) of nerve cells

Answer 6

1. Depolarisation:
   - When Na+ ions suddenly rush through open voltage-gated sodium channels into a neuron and increases the RMP.
2. Hyperpolarisation:
   - When K+ ions suddenly rush through open voltage-gated potassium channels out of a neuron and decreases the RMP.
   - When cl- ions suddenly rush through open voltage-gated cl- channels into a neuron and increases the RMP.

Question 7

What is a graded potential?

Answer 7

• Any change in electric potential of a neuron that is not propagated along the cell (as is an action potential) but declines with distance from the source.
• Shoot distance signals.

Question 8

Describe the mechanisms of action potential generation.

Answer 8

• Three steps in AP generation:
  1. Depolarisation: AP is generated when depolarisation at a certain point reaches a threshold voltage of ~ -55 mV and goes beyond it (to +30mV). Caused by influx of Na+ into neuron.
  2. Re- polarisation: caused by the closing of na+ channels and the opening of K= channels.
  3. Hyper-polarisation: occurs due to an excess of open K+ channels and K+ efflux from the cell.
• RMP is restored by Na/K pump.

Question 9

Describe the mechanisms of action potential propagation.

Answer 9

• Sudden complete depolarisation of the membrane opens more voltage-gated Na+ channels in adjacent portions of the membrane.
• A wave of depolarisation sweeps along the cell.

Question 10

What is the refractory period?

Answer 10

• Period when a further stimulus applied to a neuron (or muscle fibre) will not trigger another
  AP.
• May last 1-2 ms and its aim is to prevent back propagation of AP.

Question 11

Discuss the ‘all or none’ law of APs.

Answer 11

• As long as they reach the threshold of the cell, strong stimuli produce action potentials of the same amplitude as weak stimuli.
• APs don’t decrease in strength as they
  travel through remainder of cell membrane.
• Strength of stimulus is in the frequency of the action potentials that it generates.

Question 12

What is summation?

Answer 12

• A single excitatory postsynaptic potential unable to bring postsynaptic neuron to AP threshold.
• But postsynaptic response is result of a sum of synaptic events from many neurons.
• Two types:
  1. Temporal summation: rapid series of weak pulses from a single source into one large signal.
  2. Spatial summation: several weak signals from different locations are converted into a single larger one.

Question 13

What is an electrical synapse?

Answer 13

• Two cells are connected by gap junctions formed of channels between the cytosolic compartments of the two cells.
• It permits communication between cells by the direct propagation of ionic current from one cell to the other.

Question 14

What is a chemical synapse?

Answer 14

• Its a cell-to-cell connection via which neurotransmitters transfer nerve impulses in one way.

Question 15

What are the steps in a synaptic transmission?

Answer 15

1. AP reachesand depolarises axon terminal.
2. Depolarisation activates voltage-gated, pre-synaptic Ca2+ channels (N-type, P-Type).
3. Ca2+ entry triggers exocytosis of NTs from synaptic vesicles into the synaptic cleft, through the activation of Ca2+-sensitive fusion proteins.
4. NTs diffuse into the synaptic cleft
5. NTs bind and activate receptors on the post-synaptic membrane.
   - NT may also activate pre-synaptic NT receptors (positive or negative feedback)
6. Inactivation of NT

Question 16

What is the difference between excitatory or inhibitory synapses?

Answer 16

• NT at an excitatory synapse depolarises the postsynaptic membrane.
• E.g ACh binds to its receptors on the post-synaptic membrane activates ligand-gated Na+ channels therefore depolarising the MP.
• An NT at an inhibitory synapse hyper-polarises the postsynaptic membrane.
• E.g GABA binding to GABA receptors post-synaptic membrane activates ligand-gated Cl- channels therefore hyper-polarising the MP.

Question 17

How are NT inactivated?

Answer 17

• Inactivated/degraded by enzymes in the synaptic cleft
• Then taken up by presynaptic neuron via transporter protein & repackaged into vesicles that can be released next time an AP reaches the axon terminal.
• Alternatively taken up by glial cell and diffuse away into periphery for excretion.

Question 18

What is co-transmission?

Answer 18

• Vesicles containing classical, small molecule NTs are frequently co-released from a depolarised axon terminal with vesicles containing larger, peptide NTs.
• Fast response = classical NTs
• Slow response = peptide NTs. E.g VIP, opioids.

Question 19

Describe the mechanisms of action of local anaesthetics.

Answer 19

• Drugs target the various steps of synaptic
  transmission.
• Local anaesthetics e.g lidocaine inhibit voltage-gated Na+ channels and increases intracellular sodium concentration & promotes excitation.
• Other types of drugs:
  – Dopamine replacement therapy (L-Dopa)
  – Receptor agonists/antagonists
  – Selective serotonin reuptake inhibitors (SSRIs)

Question 20

What is myelin?

Answer 20

• A fatty sheath around axons formed by schwann cells in PNS and oligodendrocytes in CNS.
• There are high density voltage-gated Na+
  channels at gaps between myelin (nodes of ranvier).
• Saltatory conduction = AP jumping from one node to another. This allows faster propagation.

Question 21

What determines nerve conduction velocity?

Answer 21

1. Myelination:
   - Myelination = faster conduction.
2. Diameter:
   - Larger diameter = faster conduction.

Question 22

What factors interfere with nerve conduction?

Answer 22

1. Demyelination
2. Local anaesthetics inhibiting voltage gated Na+ channels thereby inhibiting formation & propagation of AP.
3. Cold.
4. Ischaemia.

Question 23

Identify and describe defects in nerve conduction in multiple sclerosis.

Answer 23

• MS is a chronic autoimmune disease where immune cells attack myelin sheaths causing demyelination.
• Results in multiple plaques of demyelination in brain and spinal cord → sclerosis.
• Interferes with AP propagation.
• Leads to fatigue, vision problems, tingling and numbness, muscle weakness, impaired balance.
• TX: Corticosteroids or immuno-modulatory/
  immuno-suppressive therapies to target inflammation/ immune response.

Question 24

What is a compound action potential?

Answer 24

• A CAP is the sum of several individual AP arising more or less simultaneously in a large number of individual axons in a stimulated, large ‘compound nerve’.
• Nerve conduction test: measures how fast an electrical impulse moves through your nerve. Therefore, the nerve is stimulated and the CAP is recorded further along the nerve