Induction and expression mechanisms of postsynaptic NMDA receptor-independent homosynaptic long-term depression

Prog Neurobiol. 2006 Jan;78(1):17-37. doi: 10.1016/j.pneurobio.2005.12.001. Epub 2006 Jan 19.


The induction of long-term depression (LTD) can be divided into two main forms, one dependent upon activation of postsynaptic NMDAR, and another independent of postsynaptic NMDAR. Non-postsynaptic NMDAR-LTD (non-NMDAR-LTD) occurs in many regions of the brain, and encompasses a wide variety of induction and expression mechanisms. In this article, the induction and expression mechanisms of such LTD in over 10 brain regions are described, with a number of common mechanisms compared across a large range of types of LTD. The article describes the involvement of different presynaptic or postsynaptic receptors in the induction of non-NMDAR-LTD, especially metabotropic glutamate receptors, cannabinoid receptors and dopamine receptors. An increase in presynaptic or postsynaptic intracellular Ca concentration is a key event in induction, commonly followed by activation of certain kinases, especially PKC, p38 MAPK and ERK. Expression mechanisms are either presynaptic via a reduction in release probability, or postsynaptic involving a decrease in AMPAR via phosphorylation of a glutamate receptor subunit, especially GluR2, followed by clathrin-mediated endocytosis. Retrograde signalling from postsynaptic to presynaptic occurs when induction is postsynaptic and expression is presynaptic.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / anatomy & histology
  • Brain / metabolism
  • Calcium / metabolism
  • Calcium Channels / metabolism
  • GTP-Binding Proteins / metabolism
  • Gene Expression Regulation
  • Long-Term Synaptic Depression / physiology*
  • Neurotransmitter Agents / metabolism
  • Nitric Oxide / metabolism
  • Protein Kinases / metabolism
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Receptors, Neurotransmitter / metabolism
  • Synapses / physiology*


  • Calcium Channels
  • Neurotransmitter Agents
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter
  • Nitric Oxide
  • Protein Kinases
  • GTP-Binding Proteins
  • Calcium