Long-term Depression (LTD)

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Long-term depression, in opposite of Long-term Potentiation (LTP), decreases the efficacy of synapse transmission due to repeated stimulation of neurons.

As in a typical axon, the neuron is depolarized due to increase in number of sodium ions. Depolarisation causes the opening of calcium ions channel on Presynaptic membrane and so calcium ions diffuse into the synapse by Facilitated diffusion. The presence of calcium ions in the synapse induces the release of Neurotransmitter into the synaptic cleft. In this case, glutamate are the neurotransmitters.

There are two types of receptor present in post-synaptic membrane, which are α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate receptor (NMDA). Glutamate binds to AMPA receptor and allows sodium ions to enter the post-synaptic membrane. Post-synaptic membrane is depolarized. NMDA remains unchanged even though glutamate have bound into the binding site because magnesium ions are present in the receptor. As time goes, the more the post-synaptic membrane gets depolarized, the magnesium ions in NMDA receptor are eventually emitted. Calcium ions that are largely present in synaptic cleft enter the post-synaptic membrane through NMDA receptor and cause sodium ions to diffuse in.

Calcium ions bind to protein kinase C and thus kinase gets phosphorylated. Phosphorylation of protein kinase C results in addition of phosphate group into AMPA receptor and makes AMPA channel more sensitive to diffusion of sodium ions. At the same time, calcium ions tend to bind to another molecule called Protein phosphatase, enzymes that pluck phosphate groups off proteins. Therefore, if LTP is putting phosphate groups on, LTD apparently is taking them off.[1]

Moreover, the induction of LTD can also be associated with the internalization of AMPA receptors at the synapse. Thus, LTP and LTD appear to reflect the bidirectional regulation of both the phosphorylation and the number of post-synaptic AMPA receptors [2].

This complementarity suggests that LTD and LTP reversibly affect synaptic efficiency by acting at a common site [3].


  1. Mark F.Bear ,Barry W.Connors ,Michael A.Paradiso ,2006:782
  2. Mark F.Bear ,Barry W.Connors ,Michael A.Paradiso ,2006:783
  3. Purves D, Augustine GJ, Fitzpatrick D, et al.,2001

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