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Proc Natl Acad Sci U S A. 2015 Jan 27;112(4):1196-201. doi: 10.1073/pnas.1416196112. Epub 2015 Jan 12.

Metabotropic glutamate receptor 3 activation is required for long-term depression in medial prefrontal cortex and fear extinction.

Author information

1
Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery and.
2
Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery and Department of Chemistry, Vanderbilt University, Nashville, TN 32027.
3
Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery and jeff.conn@vanderbilt.edu.

Abstract

Clinical studies have revealed that genetic variations in metabotropic glutamate receptor 3 (mGlu3) affect performance on cognitive tasks dependent upon the prefrontal cortex (PFC) and may be linked to psychiatric conditions such as schizophrenia, bipolar disorder, and addiction. We have performed a series of studies aimed at understanding how mGlu3 influences PFC function and cognitive behaviors. In the present study, we found that activation of mGlu3 can induce long-term depression in the mouse medial PFC (mPFC) in vitro. Furthermore, in vivo administration of a selective mGlu3 negative allosteric modulator impaired learning in the mPFC-dependent fear extinction task. The results of these studies implicate mGlu3 as a major regulator of PFC function and cognition. Additionally, potentiators of mGlu3 may be useful in alleviating prefrontal impairments associated with several CNS disorders.

KEYWORDS:

GRM3; fear extinction; group II mGlu receptors; long-term depression; medial prefrontal cortex

PMID:
25583490
PMCID:
PMC4313856
DOI:
10.1073/pnas.1416196112
[Indexed for MEDLINE]
Free PMC Article

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