Excitatory and inhibitory neurotransmission in the CNS Flashcards

1
Q

What is the typical resting membrane potential for a neuron?

A

Around 70mV

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2
Q

Describe the opening of channels in terms of direction of flow (for Na, Ca, Cl & K) for a neuron at rest

A

Na flows inwards (depolarisation)
Ca flows inwards
Cl flows inwards
K flows outwards (hyperpolarisation)

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3
Q

What would an agonist of a Na channel do?

A

Open the Na channel causes influx of Na -> excitation

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4
Q

What would a K channel antagonist do?

A

Close the K channel causing retention of K in the cell -> excitation (cell becomes more positive)

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5
Q

What would a K channel agonist do?

A

Open the K channel causing efflux of K from the cell -> inhibition (cell becomes more negative)

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6
Q

What are the functions of the 4 morphologial regions of a neuron?

A

Soma - synthetic and metabolic centre
Dendrites - receive inputs from other neurons
Axon - carries output signals to other neurons
Synapse - presynaptic cell/synaptic cleft/postsynaptic cell

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7
Q

What are the events at the synapse during neurotransmission?

A
  1. An AP depolarises the axon terminal
  2. The depolarisation opens voltage gated Ca channels and Ca enters the cell
  3. Calcium entry triggers exocytosis of synaptic vesicle contents
  4. Neurotransmitter diffuses across the synaptic cleft and binds with receptors on the postsynaptic cell
  5. Neurotransmitter binding initiates a response in the postsynaptic cell
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8
Q

What are the events involved in inactivation of neurotransmitters during neurotransmission?

A
  1. Neurotransmitters can be returned to axon terminals for reuse or transported into glial cells
  2. Enzymes inactivate neurotransmitters
  3. Neurotransmitters can diffuse out of the synaptic cleft
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9
Q

Neurotransmitters may act directly or indirectly on ion channels. Describe these 2 modes of action

A

Direct gating is by ionotropic receptors. The receptor is an integral component of the molecule that forms the channel it controls
Indirect gating is mediated by activation of metabotropic receptors. Receptor and the channel it controls are distinct

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10
Q

What is glutamate?

A

The major excitatory neurotransmitter but may also have inhibitory effects via its response at metabotropic glutamate receptors. It acts on ionotropic receptors to allow Na and Ca in and K out of the cell, net result is an EPSP, depolarisation and excitation

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11
Q

What do non-NMDA ionotropic glutamate receptors bind?

A

They bind the agonsits kainate or AMPA controlling a channel permeable to K and Na

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12
Q

What do NMDA ionotropic glutamate receptors control?

A

A channel permeable to Na, Ca, and K

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13
Q

What do non-NMDA ionotropic receptors mediate?

A

Fast excitatory synaptic transmission in the CNS

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14
Q

What do NMDA ionotropic receptors mediate?

A

Slow component to the excitatory synaptic potential

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15
Q

NMDA receptors are thought to promote neurotoxicity due to their high permeablility to what ion?

A

Calcium ions. Certain anaesthetic agents e.g. ketamine are selective blockers of NDMA operated channels

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16
Q

What are ionotropic and metabotropic glutamate receptors important for?

A

Discriminating between ON and OFF retinal pathways

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17
Q

What is GABA?

A

The main inhibitory neurotransmitter in the CNS. It acts on 2 types of receptors - ionotropic GABAa receptor (allows Cl into the cell) and metabotropic GABAb receptor (activates a K channel). Net result is an IPSP, hyperpolarisation and inhibition

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18
Q

What do benzodiazepines do in terms of GABA receptors?

A

BZDs are positive allosteric modulators of the GABAa receptor so enhance Cl entry, decrease r.m.p, and enhance inhibition in presence of GABA

19
Q

What do barbituates do in terms of GABA receptors?

A

Similar to benzodiazepines and potentiate the effect of GABA at the GABAa receptor

20
Q

What does baclofen do in terms of GABA receptors?

A

Agonist of the GABAb receptor so enhances the K current and increases inhibition

21
Q

What is glycine?

A

An inhibitory neurotransmitter acting on a glycine ionotropic receptor that gates a Cl channel. It is releaseed by interneurons in the spinal cord to inhibit antagonist muscles motor neurones

22
Q

What is the difference between ionotropic receptor gating and metabotropic receptor gating?

A

Ionotropic receptor gating of ion channels is rapid (ms), metabotropic is slower (tens or ms, ie. secs).
Ionotropic channels function as on-off switches, metabotropic receptors can act indirectly on a variety of channels and can close as well as open ion channels

23
Q

The slow actions of metabotropic receptors are insufficient to trigger an action potential, so what do they have instead?

A

Modulatory synaptic actions.

24
Q

What do modulatory synaptic actions do?

A

These act on channels in the presynaptic terminal to modulate transmitter release, modulating transmitter gated channels to regulate the size of the post-synaptic potential. This modulates the resting and voltage gated ion channels in the neuronal soma to alter e.g. resting Em potential and AP firing pattern

25
Q

Describe fast synaptic transmission

A

Fast EPSP is due to activation of ionotropic ACh receptors. Channels conduct Na and K

26
Q

Describe slow synaptic transmission

A

Slow EPSP follows activation of muscarinic (G-protein coupled) ACh receptors. ACh closes a K channel

27
Q

Name the fast mode receptor type and give some examples of receptors

A

Fast mode = ion channel receptors (ionotropic receptors) w.g. NMDA, Kainate, GABAa, Glycine, nACh, serotonin, purines

28
Q

Name the modulatory mode receptor type and give some examples of receptors

A

Modulatory mode = G-protein coupled receptors (metabotropic receptors) e.g. glutamate, GABAb, dopamine, NA, histamine, serotonin, purines and muscarinic

29
Q

What is an EPSP?

A

Excitatory post-synaptic potential - a depolarising change in rmp caused by the actions of excitatory neurotransmission . Multiple EPSPs or very large EPSPs can cause romp to cross threshold and result in an AP

30
Q

What is an IPSP?

A

Inhibitory post-synaptic potential - negative change in rmp caused by release of an inhibitory neurotransmitter. Inhibits crossing of the threshold and inhibits AP

31
Q

What is a graded potential?

A

A change in the rmp caused by an EPSP or IPSP, such a change is caused by neurotransmitter release and is not of a magnitude large enough to cross threshold and result in an AP. The strength of the potential diminishes over distance due to current leak and cytoplasmic resistance. The amplitude increases as more sodium enters, the higher the amplitude, the further the spread of the signal

32
Q

What is an interneuron?

A

A locally acting neurone, typically releases GABA and so brings about an IPSP and inhibition, function is local processing of information

33
Q

What is a projection neuron?

A

A neuron responsible for conveying signals to other parts of the brain, typically releases glutamate and so brings about an EPSP

34
Q

What does an excitatory neuron do?

A

Releases a depolarising neurotransmitter e.g. glutamate

35
Q

What does an inhibitory neuron do?

A

Releases a hyperpolarising neurotransmitter e.g. GABA

36
Q

Neurotransmitter is released in discrete packages, what are these called?

A

Quanta

37
Q

What is a quanta?

A

A quanta refers to the release of neurotransmitter from a single vesicle. The number of quanta released varies with the stimulus

38
Q

Name some strategies to increase quanta release

A

Extensive innervation e.g. Purkinje cell - inferior olivary neuron synapse or the inhibitory basket cell.
Mega humongous presynapse e.g. the Calyx of Held synapse

39
Q

Excitatory and inhibitory synapses have competitive actions. What happens during simultaneous activation of an excitatory and an inhibitory input?

A

Reduced EPSP - inhibitory input shunts the excitatory current

40
Q

What happens in the absence of an inhibitory input?

A

The neuron discharges rhythmically. An inhibitory input suppresses some action potentials resulting in a distinct pattern of discharge

41
Q

Describe synaptic integration

A

Summation of postsynaptic membrane potentials allows multiple synaptic inputs to be integrated

42
Q

What is spatial summation?

A

EPSPs and IPSPs are spatially distributed but timed together

43
Q

What is temporal summation?

A

EPSPs occur in temporal sequence such that threshold is triggered