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.
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Authors | Adam G Walker, Cody J Wenthur, Zixiu Xiang, Jerri M Rook, Kyle A Emmitte, Colleen M Niswender, Craig W Lindsley, P Jeffrey Conn |
Journal | Proceedings of the National Academy of Sciences of the United States of America
(Proc Natl Acad Sci U S A)
Vol. 112
Issue 4
Pg. 1196-201
(Jan 27 2015)
ISSN: 1091-6490 [Electronic] United States |
PMID | 25583490
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Receptors, Metabotropic Glutamate
- metabotropic glutamate receptor 3
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Topics |
- Animals
- Behavior, Animal
- Cognition
- Fear
- HEK293 Cells
- Humans
- Long-Term Synaptic Depression
- Mice
- Mice, Inbred ICR
- Mice, Knockout
- Prefrontal Cortex
(metabolism)
- Rats
- Receptors, Metabotropic Glutamate
(genetics, metabolism)
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