Induction and expression mechanisms of postsynaptic NMDA receptor-independent homosynaptic long-term depression.
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.
Anwyl
Roger
R
Department of Physiology, Trinity College, Dublin 2, Ireland. ranwyl@tcd.ie
D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D013569:Synapses / Q000502:physiology*
D015220:Calcium Channels; D018377:Neurotransmitter Agents; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D009569:Nitric Oxide; D011494:Protein Kinases; D019204:GTP-Binding Proteins; D002118:Calcium