lecture 8 - Synaptic function: Postsynaptic Flashcards
Chemical synaptic transmission
Dendritic spines are postsynaptic receivers
A dendritic spine (or spine) is a small membranous protrusion from a neuron’s dendrite that typically receives input from a single axon at the synapse.
Dendritic spines serve as a storage site for synaptic strength and help transmit electrical signals to the neuron’s cell body.
Dendritic spines have a spine neck + spine head.
Why are dendritic spines important?
They provide functional compartmentalisation.
This means that ionic and biochemical changes are partially restricted just to the activated synapse
This confers input specificity – synaptic changes occur specifically at the synapses that are activated.
Neurotransmitter receptors are in the postsynaptic density
Neurotransmitter receptors are in the postsynaptic density
Excitatory vs. inhibitory synaptic transmission
L-glutamate is a key excitatory neurotransmitter in the CNS
It is a non-essential amino acid: synthesised from glutamine by the enzyme glutaminase.
The most abundant excitatory neurotransmitter in the nervous system.
>90% of synapses in the brain signal using glutamate.
Most of these synapses form onto dendritic spines.
Key properties that indicate L-glutamate is a neurotransmi
1) Stored in synaptic vesicles – VGLUT transporters transfer glutamate from the cytosol into vesicles
2) Ca2+ dependent release (see ‘Presynaptic transmission’ lecture).
3) Specific protein targets (receptors):
Ionotropic glutamate receptors (iGluRs)
Metabotropic glutamate receptors (mGluRs).
4) Mechanism for rapid removal of transmitter from synapse → Glutamate transporters on pre- and postsynaptic neuron terminals and on astrocytes.
5) Process for glutamate synthesis within presynaptic terminals (glutamate-glutamine shuttle and metabolic processes).
Glutamate receptor subtypes
dont need to know structures or specific subtypes - just how many and
Ionotropic glutamate receptors (iGluRs)
Most glutamatergic synapses have both AMPA and NMDA classes of iGlu receptor.
AMPA receptors
NMDA receptors
AMPA receptors
Do “most of the business” of excitatory synaptic communication.
Permeable to Na+ and K+ ions.
Do not usually pass Ca2+ ions.
NMDA receptors
Activated under “special conditions”
Permeable to Ca2+ ions, as well as Na+ and K+.
This Ca2+ flux allows local biochemical changes to be triggered when NMDA receptors are activated.
General structure of a single ionotropic glutamate receptor (iGluR) subunit
iGluR subunits work together in partnerships
NMDA and AMPA receptors are tetrameric assemblies (they contain 4 subunits):
NMDA receptors are always heterotetramers (i.e. they contain at least two types of subunit)
AMPA receptors are usually heterotetramers.
Fast synaptic transmission is mediated by ionotropic receptors
NMDA receptors exhibit a voltage-dependent Mg2+ block
Mg2+ block of NMDA receptor channels is voltage dependent.
At a membrane voltage of around -35 mV, the Mg2+ block of the NMDA receptor channel is removed.
This means that inward current through NMDARs is neurotransmitter gated AND voltage dependent.
Physiological roles of NMDA receptors
NMDA receptors mediate a slow-rising, long-lasting excitatory postsynaptic current (EPSC) via Na+ and Ca2+ entry through the channel pore.
Once inside the cell, Ca2+ can modulate a range of cellular functions, such as activating enzymes, regulating ion channel opening, and altering gene expression.
This can lead to a long-lasting change in synaptic strength, termed long-term synaptic plasticity (see next lecture).
Not all synapses are exciting…
y-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain
There are two general classes of GABA receptors:
GABAA (ionotropic)
GABAB (metabotropic)
Key properties that indicate GABA is a neurotransmitter
1) Stored in synaptic vesicles – VGAT transporters transfer GABA from the cytosol into vesicles.
2) Ca2+ dependent release (see ‘Presynaptic transmission’ lecture)
3.) Specific protein targets (receptors):Ionotropic GABAA receptors
Metabotropic GABAB receptors
4) Mechanism for rapid removal of transmitter from synapse → GABA transporters (GAT1 and GAT3) on pre- and postsynaptic neuron terminals and on astrocytes.
5) Process for GABA synthesis → glutamate decarboxylase (GAD) (2 isoforms → GAD67 (expressed throughout the neuron) and GAD65 (expressed in axon terminals)).
A key difference between GABAergic and glutamatergic synapses is that GABAergic synapses do not typically form onto dendritic spines.
GABAA receptors are pentameric ligand-gated chloride channels
GABAA receptors mediate fast inhibitory synaptic transmission
Phasic inhibition hyperpolarises the postsynaptic cell – generates Inhibitory Postsynaptic Potentials (IPSPs).
GABAB receptors are heterodimeric G-protein coupled receptors
Functional receptor comprises two 7-transmembrane subunits:
GABAB1 subunit – binds to GABA
GABAB2 subunit – required for G-protein signalling (Gi/o pathway coupled)
GABAB receptors mediate slow inhibitory synaptic transmission
Coactivation of GABAARs and GABABRs produces long-lasting biphasic IPSPs
GABAB receptors are commonly found on presynaptic terminals
GABAB receptor-mediated suppression of inhibition
Postsynaptic transmission – Summary
Dendritic spines enable the functional compartmentalisation of individual synapses.
Fast excitatory synaptic transmission is largely mediated by two types of ionotropic glutamate receptor with different properties:
AMPA receptors
NMDA receptors
Inhibitory synaptic transmission largely mediated by two types of GABA receptor:
GABAA receptors: fast inhibitory transmission
GABAB receptors: slow inhibitory transmission
