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X-linked mental retardation protein is found to mediate synaptic plasticity in hippocampus
Date:10/19/2011

Cold Spring Harbor, NY Scientists at Cold Spring Harbor Laboratory (CSHL) have solved part of a puzzle concerning the relationship between changes in the strength of synapses the tiny gaps across which nerve cells in the brain communicate and dysfunctions in neural circuits that have been linked with drug addiction, mental retardation and other cognitive disorders.

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.

The result of this cascade of intracellular signals was dramatic: persistent removal of AMPA-type receptors at the excitatory synapse, and the onset of LTD. When rapid production of OPHN1 was blocked, mGluR-dependent LTD did not occur. These findings appear online today ahead of print in the journal Neuron.

Van Aelst explained the significance of the finding. "OPHN1 has two important functions that we kn
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Contact: Peter Tarr
tarr@cshl.edu
516-367-8455
Cold Spring Harbor Laboratory
Source:Eurekalert

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