Question

First, consider the cellular basis of long-term potentiation (LTP). Where in the brain does this occur and what happens? In your answer, include details of the neurotransmitters and receptors involved as well as what happens at the level of the receptor to enable LTP. Also, describe the changes that occur in both the presynaptic and post-synaptic cells as a result of LTP.

Answer 1

Answer:

Long-term potentiation (LTP) is opposite of long-term depression (LTD).The stimulus applied at a high frequency of over 100Hz but for a short duration It is a form of Synaptic plasticity in brain ,in this process a synaptic connection is formed between neurons and it become stronger with activation ,this LTP are often carried out in slices of the hippocampus, an important organ for learning and memory.LTP Involves two phases : Induction (Establishment ) It needs high frequency, it lasts for an hour involving the enzyme kinase persist after the calcium is eliminated and second phase the Expression(Maintenance) requires the synthesis of new protein which contributes for growth of new synapses. The presynaptic mechanisms contribute mostly to the late phase of compound LTP, whereas the postsynaptic mechanisms are crucial during the early phase of LTP. Protein kinase A (PKA) and gated calcium channels needed for the expression of the presynaptic LTP, and NMDA channels are essential for that of the postsynaptic component of LTP

Glutamate, the neurotransmitter released into these synapses, binds to several different sub-types of receptors on the post-synaptic neuron.

1) AMPA receptor is paired with an ion channel .Binding of this with glutamate lets sodium ions enter the post-synaptic neuron. ( dendrite depolarized ,triggers an action potential, the nerve impulse is transmitted to the next neuron)

2)NMDA receptor is also paired with an ion channel, admits calcium ions into the post-synaptic cell ,the calcium channel is blocked by (Mg2+), so that even if glutamate binds to the receptor, calcium cannot enter the neuron. the dendrite’s membrane potential must be depolarized.

In the postsynaptic neuron (depolarization to evacuate the magnesium ions that are blocking the NMDA receptor, thus allowing large numbers of calcium ions to enter the dendrite.)

Calcium ions (intracellular messengers) that activate many enzymes by altering their conformation.

Calmoduline , (activated) when four calcium ions bind to it.

Ca2+/calmodulin,(second messenger)

Activates other enzymes ( adenylate cyclase/CaM kinase II).

Modification of conformation of other molecules by adding a phosphate ion to them (phosphorylation).

Activated adenylate cyclase manufactures (cAMP) catalyzes the activity of another protein, kinase A. (PKA phosphorylates the AMPA receptors, allowing them to remain open longer after glutamate binds to them.) The postsynaptic neuron becomes further depolarized, thus contributing to LTP. .

CREB plays a major role in gene transcription, and its activation leads to the creation of new AMPA receptors that can increase synaptic efficiency

The other enzyme activated by Ca2+/calmodulin, CaM kinase II, has a property that is decisive for the persistence of LTP: it can phosphorylate itself! Its enzymatic activity continues long after the calcium has been evacuated from the cell and the Ca2+/calmodulin has been deactivated.

CaM kinase II can then in turn phosphorylate the AMPA receptors and probably other proteins such as MAP kinases, which are involved in the building of dendrites, or the NMDA receptors themselves, whose calcium conductance would be increased by this phosphorylation.