Lecture 7 - Excitatory synaptic function Flashcards
Activation of postsynaptic ionotropic glutamate receptors, causes a
transient ……..of ion channels allowing net influx of cations,
generating an …… current
opening, excitatory
…… glutamate receptors play a modulatory role in synaptic transmission
metabotropic
name 3 disorders in which glutamate plays a role in learning and memory
epilepsy, schizophrenia, brain damage
When the postsynaptic neuron is excitatory, the glutamatergic
synapse is usually found on which 2 locations of the excitatory cell?
spine or dendritic shaft
give an example of a postsynaptic excitatory neuron where the glutamatergic synapse is found on the spine or dendritic shaft
hippocampal pyramidal cell
When the postsynaptic neurons is inhibitory , the glutamatergic
synapse is usually found on which 2 locations of the inhibitory cell?
soma or dendritic shaft
give an example of a postsynaptic inhibitory interneuron on which the glutamatergic synapse is found on the soma or dendritic shaft
paralbumin-positive interneuron
name the 3 families of ionotropic glutamate receptors
AMPAR, KAINATER, NMDAR
which two classes of ionotropic glutamate receptors are mostly co-localised at glutamatergic synapses where they mediate fast chemical synaptic transmission
AMPARs and NMDARs
which class of ionotropic glutamate receptors open and close quickly and are responsible for the fast excitatory synaptic transmission in the CNS
AMPAR
which 2 ions are AMPARs permeable to, which ion are some of them permeable to?
sodium and potassium, calcium
name the 4 subunits which make up AMPARs
GluA1,2,3,4
AMPAR activity can be regulated by second messenger cascades of which kinases?
PKA, PKC, CaMKII
how many types of subunit do NDMARs have? what do they form therefore?
3, tetramers
is the activation of NMDARs slow or fast?
slow
the activation of NMDARs requires the binding of glutamate and which co-agonist?
glycine
which 3 ions do NMDARs allow the entry of into the neuron?
sodium ,potassium ,calcium
NMDARs are sensitive to ligands and…..
voltage
at RMP, NMDARs carry little current as which ions block permeability to cations? how is this block relieved?
magnesium, relieved by depolarisation
the flux of which ion through
NMDARs is thought to play
a critical role in synaptic
plasticity - the cellular
mechanism for learning
and memory?
calcium
which glutamate receptors open first, AMPA or NDMA?
AMPA
give an example of a NMDAR antagonist, making it have fast synaptic transmission
D-AP5
give an example of an AMPAR antagonist giving it slow synaptic transmission
SYM2206
…… and …….
receptors generate the large and early
component of EPSCs, whereas …….
receptors contribute to the late component
of the EPSCs
AMPA and KAINATE, NMDA
how many transmembrane domains do metabotropic glutamate receptors have and which 2 termini?
7, intracellular c and extracellular n
how many subtypes of metabotropic glutamate receptors are there which embody the 3 distinct functional groups?
8
group 1 metabotropic glutamate receptors cleave PIP2 into which 2 products? which of these products diffuses into the cytoplasm and binds ER which releases calcium?
IP3 and DAG, IP3
name the 5 effects of activating group 1 metabotropic glutamate receptors
calcium release from stores, PKC increase, homer protein release, inhibition of K+ (increases excitability), less negative membrane potential
the increase of PKC activity caused by activation of group 1 mGluRs enhances the activity of which ionotropic glutamate receptor type?
NMDAR
which protein is Important for trafficking mGluRs into and out of
synapses and functionally connect mGluRs to iGluRs?
homer protein
where are group 2 and 3 mGluRs located where they act as neuroprotective autoreceptors? what do they reduce in the terminal?
presynaptic terminals, reduce glutamate
following which two events can excitotoxicity occur from glutamate destroying neurons?
trauma or hypoxia-ischaemia
changes in synaptic efficiency can occur through which two forms? where do these occur in the brain-which part?
long term potentiation and long term depression, in hippocampus
name the 3 pathways in hippocampal formation which display long term potentiation
perforant pathway, mossy fiber pathway, schaffer collaterals
which 2 types of ionotropic glutamate receptors does the CA1 region have in the hippocampus (LTP)?
NMDA, AMPA
when the calmodulin CaMKalpha2 is blocked does it stop or start long term potentiation?
stops it
does self phosphorylation of CaMKalpha2 increase or decrease the duration of LTP?
increase
Phosphorylation by CaMaKII causes conformational changes
in which ionotropic glutamate receptor?
AMPAR
LTP at schaffer collateral CA3 synapses is due to the postsynaptic influx of which ion and the activity of what?
calcium, CaM kinase
LTP AT MOSSY FIBER (DG)–CA3 SYNAPSES IS DUE TO
……… CALCIUM INFLUX AND ……./…. PATHWAY
presynaptic, cAMP/PKA
LTP – AMPARs ……. into the postsynaptic membrane
LTD - AMPARs …… from the postsynaptic membrane
insertion, removal
growth or shrinkage of the spine from LTP/LTD occurs via the reshaping of what?
actin cytoskeleton
to initiate gene transcription which protein must CaMKalpha2 bind?
CREB protein
