Neurotransmission

Question 1

What does the whole idea of chemical neurotransmission and the vesicle hypothesis rest on?

Answer 1

• The whole idea rests on two classes of molecule: chemical messengers and chemically-gated (ligand-gated) receptors

Question 2

What compromises one motor unit? What happens if the alpha motor neuron fires an impulse? What allows for reliable transmission of excitation from neurons to cells? What does the post-synaptic part contain?

Answer 2

• Alpha motor neuron and all of the skeletal muscle fibres it innervates are one motor unit
• All motor units fire together if the alpha motor neuron fires an impulse
• High fidelity junction that allows for reliable transmission of excitation from a neuron to one cell type (e.g. a muscle fibre)
• Post-synaptic part contains lipid-bound vesicles loaded with neurotransmitter molecule (e.g. Ach)

Question 3

When is latency shortest (see diagrams)? What happens as AP is propagated away from that site?

Answer 3

• Shows that latency is shortest at the site of neuromuscular junction
• As AP is propagated away from that site, they get later and later

Question 4

What is caused in the post-synaptic cell by neurotransmitter release in the CNS?

Answer 4

-	Neurotransmitter release in the CNS causes….
o	EPSPs
o	(excitatory post-synaptic potentials)
o	&
o	IPSPs
o	(inhibitory post-synaptic potentials)
-	…in the post-synaptic cell

Question 5

How do the potentials inside an outside of cells differ in EPP, EPSP and IPSP?

Answer 5

See diagrams in lecture notes (and try to somehow make sense of them)

Question 6

What are the primary sensory neurons? What are the main neurotransmitters in CNS neurons?

Answer 6

• Primary sensory neurons: Glutamate
• CNS neurons:
   Acetylcholine
  o Amino acids:
   Gamma-aminobutyric acid (GABA) (inhibitory)
   Glycine (inhibitory)
  o Biogenic Amines:
   Noradrenaline
   5-HT
   Dopamine

Question 7

What is utilised by the stretch-reflex and reciprocal antagonist inhibition to allow for contraction of the triceps?

Answer 7

• Utilises INHIBITORY INTERNEURON – releases glycine to inhibit activity and therefore contraction at the triceps, at the same time as the biceps is activated

Question 8

How are IPSPs recorded?

Answer 8

In an antagonistic motoneuron

Question 9

What are the three types of signals in neurons and what is the speed of each?

Answer 9

Neurotransmitter (fast - ms)
Neuromodulator (slower - secs-minutes)
Neurotrophic factor (slowest - mins-hours)

Question 10

What types of signals are sent by the major neurotransmitters in the CNS?

Answer 10

• Primary sensory neurons: Glutamate (Fast + Modulator)
• CNS neurons:
• Acetylcholine (F + M)
  o Amino acids:
   Glutamate (F + M)
   Gamma-aminobutyric acid (GABA) (F + M)
   Glycine (F)
  o Biogenic Amines:
   Noradrenaline (M)
   5-HT (F + M)
   Dopamine (M)

Question 11

What type of receptors are employed by fast neurotransmission?

Answer 11

• Fast neurotransmission employs multimeric (pentameric and tetrameric) receptors that incorporate ion channels
• G-protein coupled receptors comprise 7 transmembrane spanning segments

Question 12

What are the two classes of action from neurotransmitters?

Answer 12

Direct gating of ion channel

Activation of G-protein coupled receptor

Question 13

Which neuromodulators are not fast neurotransmitters?

Answer 13

-	co-transmitter neuropeptide
o	substance P
-	e.g. inflammatory mediators etc
o	prostaglandin E2
o	bradykinin

Question 14

Which mechanisms are involved in the termination of transmitter action?

Answer 14

• Transmitter breakdown

- Reuptake using selective transport mechanisms

Question 15

What is the mechanism of neurotransmitter breakdown?

Answer 15

• e.g. Acetylcholine esterase, present in the synaptic cleft (e.g. at nerve-muscle junction)
  o can be inhibited by organophosphate nerve agents (e.g. sarin (nerve gas), insecticides)
  o medicinally inhibited by neostigmine, physostigmine etc for treatment of myasthenia gravis (pyridostigimine in Gulf War Syndrome)
• BUT ACh is unusual

Question 16

What is an example of the process of neurotransmitter reuptake?

Answer 16

• Glutamate transporters in both neurons and glia
• GABA reuptake into presynaptic terminals and astrocytes by GATs
• Biogenic amine reuptake into presynaptic terminals (e.g. for noradrenaline uptake 1 and uptake 2 mechanisms)
• All amine/amino-acid transporters utilize the
• energy stored in the Na+ gradient
• Summarized in Chapter 9 of Rang, Dale, Ritter and Moore

Question 17

What happens in the Na+/K+ dependent glutamate transporter?

Answer 17

Glutamate is taken up into pre and post-synaptic terminals, and into the adjacent glia, terminating its neurotransmitter action. The transporter uses energy stored in the transmembrane Na+ gradient to uptake glutamate.

Question 18

What are muscle action potentials recorded by electrical stimulation of the peripheral nerve?

Answer 18

• M-wave, direct activation of motor units by electrical stimulation
• H-reflex, electrical equivalent to stretch-reflex
• F-wave, antidromic motor nerve action potentials bouncing off the a-motoneurons

Question 19

What sort of abnormalities might one detect in a nerve conduction study?

Answer 19

-	Record evoked muscle action potentials –
o	Peripheral demyelination 
o	Look for giant motor units (MND/ALS)
o	Lambert-Eaton myasthenic syndrome
o	Myasthenia Gravis
o	Carpal tunnel entrapment
o	Record sensory nerve volley by recording in the digits-
o	Peripheral demyelination