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A critical role for NMDA receptors in parvalbumin interneurons for gamma rhythm induction and behavior

Abstract : Synchronous recruitment of fast-spiking parvalbumin interneurons generates gamma oscillations, rhythms that emerge during performance of cognitive tasks. Administration of NMDA receptor antagonists alters gamma rhythms, and can induce cognitive as well as psychosis-like symptoms in humans. The disruption of NMDA receptor signaling specifically in fast-spiking parvalbumin interneurons is therefore hypothesized to give rise to neural network dysfunction that could underlie these symptoms. To address the connection between NMDA receptor activity, fast-spiking parvalbumin interneurons, gamma oscillations and behavior, we generated mice lacking NMDA receptor neurotransmission only in parvalbumin cells (PV-Cre/NR1f/f mice). Here we show that mutant mice exhibit enhanced baseline cortical gamma rhythms, impaired gamma rhythm induction after optogenetic drive of parvalbumin interneurons and reduced sensitivity to the effects of NMDA receptor antagonists on gamma oscillations and stereotypies. Mutant mice show largely normal behaviors except for selective cognitive impairments, including deficits in habituation, working memory and associative learning. Our results provide evidence for the critical role of NMDA receptors in parvalbumin interneurons for expression of normal gamma rhythms and specific cognitive behaviors.
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Submitted on : Wednesday, October 5, 2011 - 2:50:08 AM
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Marie Carlen, Konstantinos Meletis, Joshua Siegle, Jessica Cardin, Kensuke Futai, et al.. A critical role for NMDA receptors in parvalbumin interneurons for gamma rhythm induction and behavior. Molecular Psychiatry, Nature Publishing Group, 2011, ⟨10.1038/mp.2011.31⟩. ⟨hal-00629065⟩

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