期刊
CEREBRAL CORTEX
卷 21, 期 3, 页码 727-735出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhq147
关键词
amygdala; fear expression; mPFC; MPEP; sAHP
资金
- National Institutes of Health [F31-GM075489, R01-MH058883, R01-MH081975]
- National Science Foundation [IOS 0842159]
- Direct For Biological Sciences
- Division Of Integrative Organismal Systems [0842159] Funding Source: National Science Foundation
Consolidation of fear extinction involves enhancement of N-methyl D aspartate (NMDA) receptor-dependent bursting in the infralimbic region (IL) of the medial prefrontal cortex (mPFC). Previous studies have shown that systemic blockade of metabotropic glutamate receptor type 5 (mGluR5) reduces bursting in the mPFC and mGluR5 agonists enhance NMDA receptor currents in vitro, suggesting that mGluR5 activation in IL may contribute to fear extinction. In the current study, rats injected with the mGluR5 antagonist 2-methyl-6-(phenylethyl)-pyridine (MPEP) systemically, or intra-IL, prior to extinction exhibited normal within-session extinction, but were impaired in their ability to recall extinction the following day. To directly determine whether mGluR5 stimulation enhances the burst firing of IL neurons, we used patch-clamp electrophysiology in prefrontal slices. The mGluR5 agonist, (RS)-2-chloro-5-hydroxyphenylglycine (CHPG), increased intrinsic bursting in IL neurons. Increased bursting was correlated with a reduction in the slow afterhyperpolarizing potential and was prevented by coapplication of MPEP. CHPG did not increase NMDA currents, suggesting that an NMDA receptor-independent enhancement of IL bursting via stimulation of mGluR5 receptors contributes to fear extinction. Therefore, the mGluR5 receptor could be a suitable target for pharmacological adjuncts to extinction-based therapies for anxiety disorders.
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