High level exam answer, Borderline first class - 2:1.
Question: Critically consider how different patterns of activity at the NMDA receptors can result in long term potentiation (LTP) or long term depression (LTD).
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Question: Critically consider how different patterns of activity at the NMDA receptors can
result in long term potentiation (LTP) or long term depression (LTD).
LTP and LTD are mechanisms by which the central nervous system can regulate and control
synaptic plasticity. The efficacy of synaptic and neural connections can be strengthened via
LTP or weakened via LTD. Both LTP and LTD can occur in many areas of the CNS but is most
commonly studied in the hippocampus in relation to explicit memory formation and in the
cerebellum, for motor learning. The processes by which LTP and LTD can arise in both the
hippocampus and cerebellum differ, but both involve the activation of glutamatergic AMPA
receptors and ca2+ ion concentration.
As mentioned, LTP and LTD in the hippocampus involve AMPA receptors but more
specifically, requires the activation of NMDA glutamatergic receptors which controls the
influx of ca2+ ions. The specific type of mechanism (LTP or LTD) that arises depends upon the
frequency of stimulation of the receptors that leads to the subsequent amount of influx of
ca2+ into the post synaptic neurone.
The hippocampus is responsible for explicit memory formation. It consists of several cell
bodies that send signals and information between each other via a loop. The entorhinal
cortex project specific information to the dentate gyrus via the performant pathway. The
dentate gyrus then projects its axons (mossy fibres) to the CA3 dendrites which in turn
sends information to the CA1 cell via the Shaffer collaterals. It is within this Shaffer
collaterals-CA1 synapse that LTP and LTD is commonly seen.
As mentioned earlier, LTP and LTD require the involvement of AMPA and NMDA receptors
on the post synaptic membrane. Both receptors are permeable to Na + ions, however, the
NMDA receptor is also permeable to ca2+ ions. The NMDA receptor is initially blocked by a
Mg2+ ion, which therefore allows little to no entry of Na+ and Ca2+ ion entry into the post
synaptic membrane.
The relative amount of sodium ion influx into the post synaptic neuron via the AMPA
receptor is determined by the frequency of stimulation of the receptors due to action
potential which leads to subsequent glutamate release. If stimulated at high frequency,
there is more glutamate release and hence, greater stimulation of AMPA receptor which
leads to greater amount of influx of sodium ions into the post synaptic neurone. A large
influx of sodium ions causes a greater degree of depolarisation in the post synaptic neurone.
This large depolarisation causes the Mg2+ blockage in the NMDA receptor to be repelled out
into the synaptic cleft vis electrostatic repulsion. This then allows for the entry of more Na +
but more importantly, the influx of Ca2+.
It has been investigated that the major determining factor whether LTP or LTD takes place is
reliant on the amount of ca2+ influx. It has been shown that small rise in ca2+ concentration
in the post synaptic neuron leads to LTD, whereas large influx of calcium contributes to LTP.
Large influx of calcium ions into the post synaptic neurone cause LTP by activating many
intracellular cascades that further strengthens the synaptic connection between neurones.
High calcium concentrations are responsible for activating calcium-calmodium dependent
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