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Synaptic Plasticity in Hippocampus Mediated By X-Linked Mental Retardation Protein
A team led by CSHL Professor Linda Van Aelst has pieced together essential steps in a signaling cascade within excitatory nerve cells that explains a key phenomenon called longterm depression, or LTD. The "depression" in question has nothing to do with the human illness with that name. Rather, it refers to a tamping-down of the strength of individual synapses what scientists call synaptic plasticity.
The mechanism behind LTD is called endocytosis. It involves a retraction of receptors where neurotransmitters can "dock." Van Aelst and colleagues have demonstrated how LTD works following activation of a class of receptors called group I metabotrobic glutamate receptors, or mGluRs.
It was known that longterm depression mediated by mGluRs depended in part on the rapid synthesis of specific proteins. Yet the identity of these proteins had largely remained a mystery. The CSHL scientists have now shown that locally rapid production of a protein called oligophrenin 1 (OPHN1) follows activation of group I mGluRs. OPHN1 in turn was shown to mediate LTD in hippocampal nerve cells, by interacting with yet another protein called EndophilinA2/3.
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