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Neuroscience > Lecture 6 - excitatory synaptic function > Flashcards

Lecture 6 - excitatory synaptic function Flashcards

1
Q

Describe glutamate.

A

the main excitatory neurotransmitter in the brain.
plays a role in learning, memory etc as well as several disorders.

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2
Q

What causes the transient opening of ion channels to allow influx of cations, generating an excitatory current?

A

activation of postsynaptic inotropic glutamate receptors.

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3
Q

What plays a role on synaptic transmission?

A

metabotropic glutamate receptors

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4
Q

Where is the glutamatergic synapse found on a postsynaptic excitatory neuron?

A

the spine or dendritic shaft of the cell

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5
Q

Where is the glutamatergic synapse found on the postsynaptic inhibitory neuron?

A

the soma or dendritic shaft of the cell

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6
Q

Describe dendritic spines.

A

on excitatory neurons
receive synaptic inputs from presynaptic axons
spines are dynamic, plastic and changeable

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7
Q

What are the 3 different types of iGluRs?

A

AMPAR, NMDAR and KainateRs

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8
Q

What iGluRs are usually co-localised at glutamatergic synapses?

A

AMPAR and NMDAR

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9
Q

What are AMPARs permeable to?

A

sodium, potassium and some of them to calcium

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10
Q

What are AMPARs formed of?

A

4 subunits - GluA1, GluA2, GluA3, GluA4

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11
Q

What can AMPAR activity be regulated by?

A

secondary messenger cascades of PKA, PKC, CaMKII and other kinases

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12
Q

What are NMDARs assembled from?

A

tetramers - formed from a choice of 3 subunits GluN1, GluN2, GluN3.

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13
Q

Do NMDARs have slow activation and deactivation kinetics or fast activation and activation kinetics?

A

Slow kinetics and deactivation kinetics.

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14
Q

What does activation of NMDARs require?

A

binding of glutamate and the co-agonist glycine

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15
Q

What ions do NMDARs allow into the cell?

A

calcium, sodium and potassium

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16
Q

Why at RMP do NMDARs carry little current?

A

magnesium ions block permeability to cations.

17
Q

What plays a key role in synaptic plasticity?

A

calcium flux through NMDARs

18
Q

Describe metabotropic receptors.

A
  • 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.
19
Q

How many subtypes of mGluRs are there?

A

8 that embody 3 distinct functional groups

20
Q

Describe the 3 steps of functional group 1 mGluRs.

A
  1. glutamate binds to the group I receptor, that is coupled to PLC.
  2. cleaves PIP2 into IP3 and DAG.
  3. IP3 diffuses to the cytoplasm and binds ER which releases calcium.
21
Q

What are the 5 effects of activation of group I mGluRs?

A
  1. calcium release from stores.
  2. PKC increase.
  3. Homer protein release.
  4. Inhibition of K conductances.
  5. Less negative membrane potential.
22
Q

What do group II/III mGluRs do?

A

reduce the amount of glutamate release from the terminal

23
Q

What is the Hebbian synapse?

A

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

24
Q

How does the Hebbian synapse permit networks to store memories?

A
  • 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
25
Q

Where does long-term potentiation occur?

A

the hippocampus

26
Q

What is the 3 synaptic circuit in the hippocampus?

A

Schaffer collateral pathway > Perforant pathway from the entorhinal cortex > Mossy fibre pathway

27
Q

What protein kinase does LTP depend on?

A

Calmodulin-dependent protein kinase (CaMKII)

28
Q

How does LTP depend on CaMKII?

A

NMDAR activation and opening allows CaMKII to be activated by high levels of calcium/CaM complexes.
Phosphorylation by CaMKII causes a conformational change in AMPARs.
This opens the pore to let more sodium in.
Series of complex reactions follow leading to the delivery and insertion of AMPA receptors into the synapse.

29
Q

What 2 cellular processes underlie the major changes during LTP and LTD?

A

LTP = AMPAR insertion into the postsynaptic membrane.

LTD = AMPAR removal from the postsynaptic membrane.

30
Q

What is LTP at mossy fibre-CA3 synapses due to?

A

presynaptic calcium influx and cAMP/PKA pathway.

Neuroscience (20 decks)

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