Long-term potentiation (LTP) and long-term depression (LTD) are two distinct forms
of synaptic plasticity that have been extensively characterized at the Schaffer collateral-CA1 (SCCA1)
synapse and the mossy fiber (MF)-CA3 synapse within the hippocampus, and are postulated
to be the molecular underpinning for several cognitive functions. Deficits in LTP and LTD have
been implicated in the pathophysiology of several neurological and psychiatric disorders.
Therefore, there has been a large effort focused on developing an understanding of the mechanisms
underlying these forms of plasticity and novel therapeutic strategies that improve or rescue these
plasticity deficits. Among many other targets, the metabotropic glutamate (mGlu) receptors show
promise as novel therapeutic candidates for the treatment of these disorders. Among the eight distinct mGlu receptor
subtypes (mGlu1-8), the mGlu1,2,3,5,7 subtypes are expressed throughout the hippocampus and have been shown to play
important roles in the regulation of synaptic plasticity in this brain area. However, development of therapeutic agents that
target these mGlu receptors has been hampered by a lack of subtype-selective compounds. Recently, discovery of
allosteric modulators of mGlu receptors has provided novel ligands that are highly selective for individual mGlu receptor
subtypes. The mGlu receptors modulate the multiple forms of synaptic plasticity at both SC-CA1 and MF synapses and
allosteric modulators of mGlu receptors have emerged as potential therapeutic agents that may rescue plasticity deficits
and improve cognitive function in patients suffering from multiple neurological and psychiatric disorders.
Keywords: Allosteric, hippocampus, long term potentiation, long term depression, mGlu, mGluR, mossy fiber, SC-CA1.
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