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what is a dendritic spine?
a small membranous protrusion from a neuron's dendrite that typically receives input from a single axon at the synapse
what is the function of a dendritic spine?
act as a storage site for synaptic strength and help transmit electrical signals to the neuron's cell body
what is the structure of a dendritic spine?
they have a spine neck and a spine head
why are dendritic spines important?
they provide functional compartmentalisation, meaning ionic and biochemical changes are partially restricted just to the activated synapse (causing input specificity)
what is the postsynaptic density?
a network of proteins that regulate and anchor neurotransmitter receptors
what generates an Excitatory Post-Synaptic Potential (EPSP)?
net movement of cations into the post-synaptic cell- as it depolarises membrane potential
what generates an Inhibitory Post-Synaptic Potential (IPSP)?
net movement of anions into the post-synaptic cell OR cations out of the post-synaptic cell- as it hyperpolarises membrane potential
what is glutamate synthesised from?
glutamine by the enzyme glutaminase
what are the 5 key properties that indicate a substance is a neurotransmitter?
1) stored in synaptic vesicles 2) Ca2+ dependant release 3) specific protein targets 4) mechanism for rapid removal of transmitter from synapse 5) process for synthesis within pre-synaptic terminals
what are the key properties that indicate L-Glutamate is a neurotransmitter?
1) stored in synaptic vesicles- transporters transfer glu from the cytosol into vesicles 2) Ca2+ dependant release 3) specific protein targets- iGluRs & mGluRs 4) mechanism for rapid removal of transmitter from synapse- Glu transporters on pre&postsynaptic terminals and on astrocytes 5) process for synthesis within pre-synaptic terminals (glutamine->glutamate)
what receptors at glutamatergic synapses contribute the most to excitatory synaptic communication?
AMPA receptors
what is AMPA receptors permeable to?
Na+ and K+
what are NMDA receptors permeable to?
Ca2+, Na+, and K+
what does NMDA being permeable to Ca2+ do?
Ca2+ flux allows local biochemical changes to be triggered when NMDA receptors activate
how many subunits do both NMDA and AMPA contain?
4
what is a heterotetramer?
contain at least 2 types of subunits
out of NMDA & AMPA receptors, which is always a heterotetramer?
NMDA
Which subunit of AMPA receptors, is impermeable to Ca2+
GluA2
Describe Mg2+ block of the NMDAR pore:
the Mg2+ block is voltage-dependant: at depolarised potentials the Mg2+ block of the NMDA receptor is removed
what does the Mg2+ block of NMDA receptors being voltage-dependant mean?
that the inward current through NMDARs is neurotransmitter gated and voltage dependent
what do NMDA receptors mediate?
slow-rising, long lasting excitatory postsynaptic current (ESPC) via Na+ and Ca2+ entry through the channel pore
once inside a cell/NMDA receptor, what cellular functions can it modulate?
activating enzymes, regulating ion channel opening, and altering gene expression
what does Ca2+ altering cell/NMDA receptors functions, result in?
long-lasting synaptic strength= long-term synaptic plasticity
what are the 2 classes of GABA receptors?
GABAa= ionotropic GABAb= metabotropic
what is GABA's real name?
y-aminobutyric acid
what is the 5 key properties that indicate GABA is a neurotransmitter?
1) stored in vesicles- VGAT transporters transfer GABA from cytosol into vesicles 2) Ca2+ dependent release 3) Has specific protein targets: GABAa & GABAb 4) mechanism for rapid synapse removal- GABA transporters on pre&postsynaptic terminals and astrocytes 5) process for GABA synthesis
what is a key difference between GABAergic and Glutamatergic synapses?
GABAergic synapses do not typically form onto dendritic spines
how many subunits are GABAa made up of?
5, is pentametric
what type of channel are GABAa receptors?
pentameric ligand-gated chloride channels
what flows into GABAa receptors, and how?
Cl- flow along their electrochemical gradient into the cell, hyperpolarising it
what type of receptor is GABAb receptors?
heterodimeric G-protein coupled receptors
what does the GABAb1 subunit do?
bind to GABA
what does the GABAb2 subunit do?
G-protein signalling (coupled with the Gi/o pathway)
what type of synaptic transmission does GABAb receptors mediate?
slow inhibitory synaptic transmission
how does GABAb mediate slow inhibitory transmission?
activating GIRK K+ channels, so K+ slowly flows out of the cell- hyperpolarising it
what GABA receptor is fast and which is slow, IPSP?
GABAa= fast GABAb= slow
what is an autoreceptor?
a receptor found on the presynaptic terminal that is activated by the neurotransmitter released by the same synapse
which GABA receptor is an autoreceptor?
GABAb
what can GABAb autoreceptors present result in?
a form of paired prepulse depression
describe the 4 step process of GABAb receptor-mediated suppression of inhibition?
1) GABAb receptors couple to Gi/o G-protein signalling 2) activation of presynaptic GABAb receptors inhibit presynaptic vgCa2+ channels 3) restricting Ca2+ entry into the presynaptic terminal 4) Resulting in the 2nd stimulus having reduced Ca2+ dependent exocytosis= less GABA released