Lecture 6 - excitatory synaptic function Flashcards
Describe glutamate.
the main excitatory neurotransmitter in the brain.
plays a role in learning, memory etc as well as several disorders.
What causes the transient opening of ion channels to allow influx of cations, generating an excitatory current?
activation of postsynaptic inotropic glutamate receptors.
What plays a role on synaptic transmission?
metabotropic glutamate receptors
Where is the glutamatergic synapse found on a postsynaptic excitatory neuron?
the spine or dendritic shaft of the cell
Where is the glutamatergic synapse found on the postsynaptic inhibitory neuron?
the soma or dendritic shaft of the cell
Describe dendritic spines.
on excitatory neurons
receive synaptic inputs from presynaptic axons
spines are dynamic, plastic and changeable
What are the 3 different types of iGluRs?
AMPAR, NMDAR and KainateRs
What iGluRs are usually co-localised at glutamatergic synapses?
AMPAR and NMDAR
What are AMPARs permeable to?
sodium, potassium and some of them to calcium
What are AMPARs formed of?
4 subunits - GluA1, GluA2, GluA3, GluA4
What can AMPAR activity be regulated by?
secondary messenger cascades of PKA, PKC, CaMKII and other kinases
What are NMDARs assembled from?
tetramers - formed from a choice of 3 subunits GluN1, GluN2, GluN3.
Do NMDARs have slow activation and deactivation kinetics or fast activation and activation kinetics?
Slow kinetics and deactivation kinetics.
What does activation of NMDARs require?
binding of glutamate and the co-agonist glycine
What ions do NMDARs allow into the cell?
calcium, sodium and potassium
Why at RMP do NMDARs carry little current?
magnesium ions block permeability to cations.
What plays a key role in synaptic plasticity?
calcium flux through NMDARs
Describe metabotropic receptors.
- single polypeptide chain proteins that bind glutamate.
- they have 7 transmembrane domains with an intracellular C termini and extracellular N termini
- link glutamate binding to the activation of G-proteins mediated by signalling cascades.
How many subtypes of mGluRs are there?
8 that embody 3 distinct functional groups
Describe the 3 steps of functional group 1 mGluRs.
- glutamate binds to the group I receptor, that is coupled to PLC.
- cleaves PIP2 into IP3 and DAG.
- IP3 diffuses to the cytoplasm and binds ER which releases calcium.
What are the 5 effects of activation of group I mGluRs?
- calcium release from stores.
- PKC increase.
- Homer protein release.
- Inhibition of K conductances.
- Less negative membrane potential.
What do group II/III mGluRs do?
reduce the amount of glutamate release from the terminal
What is the Hebbian synapse?
when an axon of cell A is near enough to excite cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A’s efficiency, as one of the cells firing B, is increased
How does the Hebbian synapse permit networks to store memories?
- synapse strengthened by repeated activity
- Hebbian synapse is a coincidence detector
- NMDARs, back-propagating APs and summation of EPSPs appear to be the components that confer Hebbian behaviour on the synapse.
- changes in synaptic efficiency cause either long-term potentiation or long-term depression
