title: Metabotropic glutamate receptor 3 activation is required for long-term depression in medial prefrontal cortex and fear extinction.
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.
authors.affiliation: Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery and.
authors.forename: Adam G
authors.initials: AG
authors.lastname: Walker
authors.affiliation: Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery and.
authors.forename: Cody J
authors.initials: CJ
authors.lastname: Wenthur
authors.affiliation: Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery and.
authors.forename: Zixiu
authors.initials: Z
authors.lastname: Xiang
authors.affiliation: Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery and.
authors.forename: Jerri M
authors.initials: JM
authors.lastname: Rook
authors.affiliation: Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery and Department of Chemistry, Vanderbilt University, Nashville, TN 32027.
authors.forename: Kyle A
authors.initials: KA
authors.lastname: Emmitte
authors.affiliation: Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery and.
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Niswender
authors.affiliation: Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery and Department of Chemistry, Vanderbilt University, Nashville, TN 32027.
authors.forename: Craig W
authors.initials: CW
authors.lastname: Lindsley
authors.affiliation: Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery and jeff.conn@vanderbilt.edu.
authors.forename: P Jeffrey
authors.initials: PJ
authors.lastname: Conn
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D003071:Cognition; D005239:Fear; D057809:HEK293 Cells; D006801:Humans; D036881:Long-Term Synaptic Depression; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D017397:Prefrontal Cortex / Q000378:metabolism*; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism*
chemical_list: D018094:Receptors, Metabotropic Glutamate; C102718:metabotropic glutamate receptor 3
keywords: GRM3; fear extinction; group II mGlu receptors; long-term depression; medial prefrontal cortex