Article

The regulation of hippocampal LTP by the molecular switch, a form of metaplasticity, requires mGlu5 receptors.

MRC Centre for Synaptic Plasticity, Department of Anatomy, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK.
Neuropharmacology (impact factor: 4.81). 02/2005; 49 Suppl 1:13-25. DOI:10.1016/j.neuropharm.2005.05.020 pp.13-25
Source: PubMed

ABSTRACT The role of metabotropic glutamate (mGlu) receptors in long-term potentiation (LTP) in the hippocampus is controversial. In the present study, we have used mice in which the mGlu1, mGlu5 or mGlu7 receptor has been deleted, by homologous recombination, to study the role of these receptor subtypes in LTP at CA1 synapses. We investigated the effects of the knockouts on both LTP and the molecular switch, a form of metaplasticity that renders LTP insensitive to the actions of the mGlu receptor antagonist MCPG ((S)-alpha-methyl-4-carboxyphenylglycine). We find that LTP is readily induced in the three knockouts and in an mGlu1 and mGlu5 double knockout. In addition, the molecular switch operates normally in either the mGlu1 or mGlu7 knockout. In contrast, the molecular switch is completely non-functional in the mGlu5 knockout, such that MCPG invariably blocks the induction of additional LTP in an input where LTP has already been induced. The effect of the mGlu5 receptor knockout was replicated in wildtype mouse slices perfused with the specific mGlu5 receptor antagonist MPEP (2-methyl-6-(phenylethynyl)-pyridine). In addition, the mGlu5 selective agonist CHPG ((RS)-2-chloro-5-hydroxyphenylglycine) sets the molecular switch. These data demonstrate that the operation of the molecular switch requires activation of mGlu5 receptors.

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Keywords

additional LTP
 
CA1 synapses
 
homologous recombination
 
long-term potentiation
 
metabotropic glutamate
 
metaplasticity
 
mGlu receptor antagonist MCPG
 
mGlu1
 
mGlu5 double knockout
 
mGlu5 knockout
 
mGlu5 receptor knockout
 
mGlu5 receptors
 
mGlu5 selective agonist CHPG
 
mGlu7 receptor
 
receptor subtypes
 
renders LTP insensitive
 
RS)-2-chloro-5-hydroxyphenylglycine
 
specific mGlu5 receptor antagonist MPEP
 
three knockouts
 
wildtype mouse slices perfused