Excitatory and inhibitory neurotransmission in the CNS Flashcards
Na+ channels.
Flow inwards.
- Depolarisation.
- Excitatory.
Ca2+ channels.
Flow inwards.
- Depolarisation.
- Excitatory.
Cl- channels.
Flow inwards.
- Hyperpolarisation.
- Inhibitory.
K+ channels.
Flow outwards.
- Hyperpolarisation.
- Inhibitory.
Na+ channel agonists act to cause?
Excitation.
Na+ channel antagonists act to cause?
Inhibition.
Give an example of a Na+ channel antagonist.
Local anaesthetics e.g. Lidocaine.
K+ channel agonists act to cause?
Inhibition.
K+ channel antagonists act to cause?
Excitation.
Neuron structure can be divided into four morphological regions, which are?
- soma
- dendrites
- axon
- synapse
What part of the neuron receives incoming signals?
Dendrites.
What part of the neuron carries outgoing information?
Axons.
What are the two major families of ligand-gated channels?
- Nicotinic, GABAa, Glycine receptors.
- Glutamate receptors.
Glutamate is the major excitatory neurotransmitter but may also have inhibitory effects via its response at which receptors?
Metabotropic Glutamate receptors.
How may Ionotropic glutamate receptors be classified?
Via their response to non-endogenous agonists mimicing glutamate.
- non-NMDA.
- NMDA
Non-NMDA receptors bind what to control what?
Agonists Kainate or AMPA to control a channel permeable to Na+ and K+.
NMDA receptors control what?
A channel permeable to Na+, Ca2+ and K+.
Non-NMDA ionotropic receptors mediate what?
Fast excitatory synaptic transmission in the CNS.
NMDA receptors contribute what to the excitatory synaptic potential?
The slow component.
NMDA have a high permeability to what?
Ca2+.
NMDA’s high Ca2+ permeability is thought to promote what?
Neurotoxicity.
Ketamine and psychomimetric agents e.g. phencyclidine are selective blockers of what channels?
NMDA-operated channels.
How do metabotropic glutamate receptors exert their effect as they do not have an integral ion channel?
Activation of a second messenger cascade.
What is the role of metabotropic glutamate receptors?
Modulation of neurotransmission.
Give an example of how metabotropic glutamate receptors modulate neurotransmission?
Presynaptic inhibtion e.g. inhibition of Ca2+ channels.
What is the main inhibitory neurotransmitter in the CNS?
GABA.
Which 2 types of receptors does GABA act on?
- Ionotropic GABAa receptor.
- Metabotropic GABAb receptor.
An Ionotropic GABAa receptor operates what type of channel?
Cl- channel
A Metabotropic GABAb receptor often activates what type of channel?
K+ channel.
Benzodiazepines are what to GABAa receptors?
Positive allosteric modulators.
Benzodiazepines act on GABAa receptors to do what?
- Enhance Cl- entry.
- Decrease rmp.
- Enhance inhibition in the presence of GABA.
Barbituates have what effect at the GABAa receptor?
Potentiate the effect of GABA.
Baclofen acts on the GABAb receptor as what?
An agonist to enhance the K+ current and thus increase inhibition.
Glycine is an inhibitory neurotransmitter that acts on what receptor?
Glycine ionotropic receptor that gates a Cl- channel.
What releases glycine?
Interneurones in the spinal cord to inhibit antagonist muscle motoneurones.
Describe the speed of ionotropic receptor gating of ion channels?
Rapid
Describe the speed of metabotropic receptor gating of ion channels?
Slow (-er than ionotropic).
What action do metabotropic receptors typically have?
Modulatory synaptic actions.
Metabotropic and ionotropic receptors act on channels in the presynaptic terminal to modulate what?
Transmitter release.
Metabotropic and ionotropic receptors modulate transmitter-gated channels to regulate what?
The size of the post-synaptic potential.
Metabotropic and ionotropic receptors modulate the resting and voltage-gated ion channels in the neuronal soma to alter what?
Resting Em and AP firing pattern.
Cholinergic synaptic transmission in the autonomic ganglia display both what actions?
Direct and indirect.
Fast EPSP is due to activation of what?
Nicotinic (ionotropic) ACh receptors - channels that conduct Na+ and K+.
Slow EPSP follows activation of what?
Muscarinic receptros.
What does EPSP stand for?
excitatory post synaptic potential
What is EPSP?
Depolarising change in rmp due to excitatory neurotransmission.
Multiple/very large EPSP may cause what?
RMP to cross threshold and result in an action potential.
What is an inhibitory post synaptic potential (IPSP)?
Negative change in rmp due to inhibitory neurotransmitter release.
What does IPSP inhibit?
rmp crossing threshold thus inhibiting an action potential.
what is graded potential?
Change in rmp due to EPSP or IPSP.
Changes in rmp due to EPSP/IPSP are caused by what?
Release of excitatory/inhibitory neurotransmitters.
What receives the stimulus in a graded potential?
Cell body.
The strength of a graded potential is determined by what?
How much charge enters the cell.
Why does the strength of a graded potential diminish over distance?
Due to current leak and cytoplasmic resistance.
What causes increase in amplitude of a graded potential?
Sodium entering.
As amplitude of a graded potential increases, what happens to the spread of signal?
It goes further.
What is the result of a graded potential that does not go beyond threshold at the trigger zone?
No action potential will be generated.
What is glutamate?
The major excitatory neurotransmitter.
What does glutamate act on?
Ionotropic receptrs to allow Na+ and Ca2+ in, and K+ out of the cell.
What is the net result of Glutamate’s action?
- EPSP.
- Depolarisation.
Excitation.
What is GABA?
The major inhibitory neurotransmitter.
What does GABA act on?
Ionotropic receptors to allow Cl- into the cell.
What is the net result of GABA’s action?
- IPSP.
- Hyperpolarisation.
- Inhibition.
What is an interneurone?
A locally acting neurone that typically releases GABA.
What is the function of an interneurone?
- GABA release 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.
A projection neurone typically release what?
Glutamate to bring about an EPSP.
Excitatory neurones release what?
A depolarising neurotransmitter e.g. glutamate.
Glutamate is an example of what kind of neurotransmitter?
Depolarising/excitatory.
GABA is an example of what kind of neurotransmitter?
Hyperpolarising/inhibitory.
The influence of a synapse depends on what?
The distance the current has to travel to the neurones trigger zone.
Neurotransmitter is released in discrete packages called what?
Quanta.
A quanta refers to what/
The release of a neurotransmitter from a single vesicle.
The number of quanta released varies with what?
The stimulus.
Name a strategy to increase quantal release.
- Extensive innervation.
- Megahumongous presynapse.
Give an example of extensive innervation to increase quantal release.
- Purkinje cell - Inferior Olivary Neuron Synapse.
- The inhibitory basket cell (common in cerebellum, hippocampus and cortex).
Give an example of a megahumungous presynapse.
- Calyx of Held synapse.
Describe the relationship between purkinje cells and parallel fibres.
A single Purkinje cell is contacted by approx. 400 parallel fibres. These fibres contact multiple Purkinje cells.
Purkinje cells are innervated by parallel fibres and what else?
Climbing fibre.
Activation of an excitatory input produces what?
A large EPSP at the trigger zone- initial segment.
Cation selective channels Na+ and K+.
Activation of an inhibitory input produces what?
A large IPSP at the initial segment (opens Cl- channels).
Simultaneous activation of excitatory and inhibitory input results in what?
Reduced EPSP as the inhibitory input shunts the excitatory current.
In the absence of inhibitory input, what happens to a spontaneously active neurone?
It discharges rhythmically.
In the presence of inhibitory input, what happens to a spontaneously active neurone?
A distinct pattern of discharge.
Summation of postsynaptic membrane potentials allows what?
Multiple synaptic inputs to be integrated.
Describe spatial summation.
EPSPs and IPSPs are spatially distributed but timed together.
Describe temporal summation.
EPSPs occur in temporal sequence to trigger threshold.
