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Cerebral Cortex Advance Access published online on January 11, 2006

Cerebral Cortex, doi:10.1093/cercor/bhj103
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© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Article

Metabotropic Glutamate Receptors Modulate the NMDA- and AMPA-Induced Gene Expression in Neocortical Interneurons

Kerstin Lindemeyer 1, Jost Leemhuis 1, Steffen Löffler 1, Nina Grass 1, Wolfgang Nörenberg 2, and Dieter K. Meyer 1 *

1 Institute of Experimental and Clinical Pharmacology and Toxicology, Albert Ludwigs University, Freiburg, Germany
2 Rudolf-Boehm-Institute of Pharmacology, University of Leipzig, Leipzig, Germany

* To whom correspondence should be addressed.
Dieter K. Meyer, E-mail: dieter.meyer{at}pharmakol.uni-freiburg.de


   Abstract

Group I metabotropic glutamate receptors (mGluRIs) can be colocalized with ionotropic glutamate receptors in postsynaptic membranes. We have investigated whether mGluRIs alter the gene transcription induced by N-methyl-D-aspartate (NMDA) and (S)-{alpha}-amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid (AMPA) receptors in rat neocortical {gamma}-aminobutyric acid (GABA) interneurons. In cultures of dissociated interneurons, the mGluRI antagonists LY367385 and MPEP reduced the increase in phosphorylation of the transcription factor CREB induced by NMDA as well as the expression of the proenkephalin (PEnk) gene. In contrast, they enhanced the AMPA-induced CREB phosphorylation and PEnk gene expression. Stimulation of the mGluRIs was due to network activity that caused the release of endogenous glutamate and could be blocked by tetrodotoxin. In organotypic cultures of neocortex, endogenous glutamate enhanced the PEnk gene expression by acting on NMDA and AMPA receptors. These effects were modulated via mGluRIs. In patch-clamp experiments and in biochemical studies on receptor density, stimulation of mGluRIs acutely affected NMDA receptor currents but had no long-term effect on NMDA receptor density at the cell surface. In contrast, stimulation of mGluRIs decreased the density of AMPA receptors located at the cell surface. Our results suggest that mGluRIs regulate the glutamate-induced gene expression in neocortical interneurons in a physiologically relevant manner.

Keywords: CREB; GluR1 subunit; glutamate; MPEP; NR1 subunit.
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