title: A critical role for NMDA receptors in parvalbumin interneurons for gamma rhythm induction and behavior.
abstract: Synchronous recruitment of fast-spiking (FS) parvalbumin (PV) interneurons generates gamma oscillations, rhythms that emerge during performance of cognitive tasks. Administration of N-methyl-D-aspartate (NMDA) receptor antagonists alters gamma rhythms, and can induce cognitive as well as psychosis-like symptoms in humans. The disruption of NMDA receptor (NMDAR) signaling specifically in FS PV interneurons is therefore hypothesized to give rise to neural network dysfunction that could underlie these symptoms. To address the connection between NMDAR activity, FS PV interneurons, gamma oscillations and behavior, we generated mice lacking NMDAR neurotransmission only in PV 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 PV interneurons and reduced sensitivity to the effects of NMDAR 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 NMDAR in PV interneurons for expression of normal gamma rhythms and specific cognitive behaviors.
authors.affiliation: Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, MIT, Cambridge, MA 02139, USA. marie.carlen@ki.se
authors.forename: M
authors.initials: M
authors.lastname: Carlén
authors.forename: K
authors.initials: K
authors.lastname: Meletis
authors.forename: J H
authors.initials: JH
authors.lastname: Siegle
authors.forename: J A
authors.initials: JA
authors.lastname: Cardin
authors.forename: K
authors.initials: K
authors.lastname: Futai
authors.forename: D
authors.initials: D
authors.lastname: Vierling-Claassen
authors.forename: C
authors.initials: C
authors.lastname: Rühlmann
authors.forename: S R
authors.initials: SR
authors.lastname: Jones
authors.forename: K
authors.initials: K
authors.lastname: Deisseroth
authors.forename: M
authors.initials: M
authors.lastname: Sheng
authors.forename: C I
authors.initials: CI
authors.lastname: Moore
authors.forename: L-H
authors.initials: LH
authors.lastname: Tsai
mesh_terms: D000818:Animals; D001245:Association Learning / Q000187:drug effects / Q000502:physiology*; D058256:Brain Waves / Q000187:drug effects / Q000502:physiology*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D059330:GABAergic Neurons / Q000378:metabolism / Q000502:physiology*; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D010320:Parvalbumins / Q000378:metabolism; D010775:Photic Stimulation / Q000379:methods; D010852:Picrotoxin / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D055139:Sensory Gating / Q000187:drug effects / Q000502:physiology; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology
chemical_list: D018756:GABA Antagonists; D010320:Parvalbumins; D010852:Picrotoxin; D016194:Receptors, N-Methyl-D-Aspartate; C409466:NR1 NMDA receptor