Excitatory and inhibitory neurotransmission in the CNS Flashcards
What is the typical resting membrane potential for a neuron?
Around 70mV
Describe the opening of channels in terms of direction of flow (for Na, Ca, Cl & K) for a neuron at rest
Na flows inwards (depolarisation)
Ca flows inwards
Cl flows inwards
K flows outwards (hyperpolarisation)
What would an agonist of a Na channel do?
Open the Na channel causes influx of Na -> excitation
What would a K channel antagonist do?
Close the K channel causing retention of K in the cell -> excitation (cell becomes more positive)
What would a K channel agonist do?
Open the K channel causing efflux of K from the cell -> inhibition (cell becomes more negative)
What are the functions of the 4 morphologial regions of a neuron?
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
What are the events at the synapse during neurotransmission?
- An AP depolarises the axon terminal
- The depolarisation opens voltage gated Ca channels and Ca enters the cell
- Calcium entry triggers exocytosis of synaptic vesicle contents
- Neurotransmitter diffuses across the synaptic cleft and binds with receptors on the postsynaptic cell
- Neurotransmitter binding initiates a response in the postsynaptic cell
What are the events involved in inactivation of neurotransmitters during neurotransmission?
- Neurotransmitters can be returned to axon terminals for reuse or transported into glial cells
- Enzymes inactivate neurotransmitters
- Neurotransmitters can diffuse out of the synaptic cleft
Neurotransmitters may act directly or indirectly on ion channels. Describe these 2 modes of action
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
What is glutamate?
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
What do non-NMDA ionotropic glutamate receptors bind?
They bind the agonsits kainate or AMPA controlling a channel permeable to K and Na
What do NMDA ionotropic glutamate receptors control?
A channel permeable to Na, Ca, and K
What do non-NMDA ionotropic receptors mediate?
Fast excitatory synaptic transmission in the CNS
What do NMDA ionotropic receptors mediate?
Slow component to the excitatory synaptic potential
NMDA receptors are thought to promote neurotoxicity due to their high permeablility to what ion?
Calcium ions. Certain anaesthetic agents e.g. ketamine are selective blockers of NDMA operated channels
What are ionotropic and metabotropic glutamate receptors important for?
Discriminating between ON and OFF retinal pathways
What is GABA?
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
What do benzodiazepines do in terms of GABA receptors?
BZDs are positive allosteric modulators of the GABAa receptor so enhance Cl entry, decrease r.m.p, and enhance inhibition in presence of GABA
What do barbituates do in terms of GABA receptors?
Similar to benzodiazepines and potentiate the effect of GABA at the GABAa receptor
What does baclofen do in terms of GABA receptors?
Agonist of the GABAb receptor so enhances the K current and increases inhibition
What is glycine?
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
What is the difference between ionotropic receptor gating and metabotropic receptor gating?
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
The slow actions of metabotropic receptors are insufficient to trigger an action potential, so what do they have instead?
Modulatory synaptic actions.
What do modulatory synaptic actions do?
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
Describe fast synaptic transmission
Fast EPSP is due to activation of ionotropic ACh receptors. Channels conduct Na and K
Describe slow synaptic transmission
Slow EPSP follows activation of muscarinic (G-protein coupled) ACh receptors. ACh closes a K channel
Name the fast mode receptor type and give some examples of receptors
Fast mode = ion channel receptors (ionotropic receptors) w.g. NMDA, Kainate, GABAa, Glycine, nACh, serotonin, purines
Name the modulatory mode receptor type and give some examples of receptors
Modulatory mode = G-protein coupled receptors (metabotropic receptors) e.g. glutamate, GABAb, dopamine, NA, histamine, serotonin, purines and muscarinic
What is an EPSP?
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
What is an IPSP?
Inhibitory post-synaptic potential - negative change in rmp caused by release of an inhibitory neurotransmitter. Inhibits crossing of the threshold and inhibits AP
What is a graded potential?
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
What is an interneuron?
A locally acting neurone, typically releases GABA and so brings about an IPSP and inhibition, function is local processing of information
What is a projection neuron?
A neuron responsible for conveying signals to other parts of the brain, typically releases glutamate and so brings about an EPSP
What does an excitatory neuron do?
Releases a depolarising neurotransmitter e.g. glutamate
What does an inhibitory neuron do?
Releases a hyperpolarising neurotransmitter e.g. GABA
Neurotransmitter is released in discrete packages, what are these called?
Quanta
What is a quanta?
A quanta refers to the release of neurotransmitter from a single vesicle. The number of quanta released varies with the stimulus
Name some strategies to increase quanta release
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
Excitatory and inhibitory synapses have competitive actions. What happens during simultaneous activation of an excitatory and an inhibitory input?
Reduced EPSP - inhibitory input shunts the excitatory current
What happens in the absence of an inhibitory input?
The neuron discharges rhythmically. An inhibitory input suppresses some action potentials resulting in a distinct pattern of discharge
Describe synaptic integration
Summation of postsynaptic membrane potentials allows multiple synaptic inputs to be integrated
What is spatial summation?
EPSPs and IPSPs are spatially distributed but timed together
What is temporal summation?
EPSPs occur in temporal sequence such that threshold is triggered
