Cited by 669Neuroscience and Neuropharmacology ResearchNeural dynamics and brain functionGenetics and Neurodevelopmental Disorders

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

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Carlén, M, Meletis, K, Siegle, J H, Cardin, J A, Futai, K, Vierling-Claassen, D, Rühlmann, C, Jones, S R +4 more·2012·Molecular Psychiatry

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.

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Crossref · 10.1038/mp.2011.31

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  • NMDA receptors in PV-INs regulate gamma rhythms and cognitive behaviors.

    “Importantly, NMDA receptors in PV-INs are regulating gamma rhythms and cognitive behaviors [121].”

    From Parvalbumin interneuron vulnerability and brain disorders (2021) · cites this paper as [121]

  • Optic stimulation of PV interneurons in mice with reduced NR1 expression reveals diminished spike synchronization as well as increased spike latency and variance in spike timing.

    “Optic stimulation of PV interneurons revealed diminished spike synchronization as well as increased spike latency and variance in spike timing.”
  • Mice with a reduced expression of NMDA NR1 subunits on PV interneurons are characterized by increased spontaneous 36-44 Hz activity in somatosensory cortex compared to control animals while showing reduced gamma-band activity during sensory stimulation.

    “Mice with a reduced expression of NR1 subunits were characterized by increased spontaneous 36–44 Hz activity in somatosensory cortex compared to control animals while showing reduced gamma-band activity during sensory stimulation which was accompanied by dysfunctions in habituation, working memory, and associative learning.”
  • Mice with reduced NR1 expression on PV interneurons show dysfunctions in habituation, working memory, and associative learning.

    “Mice with a reduced expression of NR1 subunits were characterized by increased spontaneous 36–44 Hz activity in somatosensory cortex compared to control animals while showing reduced gamma-band activity during sensory stimulation which was accompanied by dysfunctions in habituation, working memory, and associative learning.”
  • Pharmacological and genetic manipulations leading to downregulation of NMDA-receptor activity consistently increase gamma-band activity during rest.

    “Pharmacological and genetic manipulations leading to a downregulation of NMDA-receptor activity have consistently demonstrated an increase of gamma-band activity during rest”

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Authors
Carlén, M., Meletis, K., Siegle, J. H., Cardin, J. A., Futai, K., Vierling-Claassen, D., Rühlmann, C., Jones, S. R., Deisseroth, K., Sheng, M., Moore, C. I., & Tsai, L.-H.
Affiliations
  • Massachusetts Institute of Technology (US)
  • Karolinska Institutet (SE)
  • McGovern Institute for Brain Research (US)
  • Harvard University (US)
  • Stanford University (US)
  • Broad Institute (US)
Corresponding author
  • Carlén, M
  • Moore, C I
  • Tsai, L-H
Venue
Molecular Psychiatry
Published
2011-04-05
Volume
17
Issue
5
Pages
537-548
ISSN
  • 1359-4184 (ISSN-L)
  • 1476-5578
OpenAlex
W2152511855
Cited by
669
References
67
Citations by year
2026: 33 · 2025: 49 · 2024: 46 · 2023: 34 · 2022: 36 · 2021: 56 · 2020: 50 · 2019: 45 · 2018: 52 · 2017: 38 · 2016: 42 · 2015: 62 · 2014: 48 · 2013: 43 · 2012: 25
FWCI
16.69
Type
journal article
Language
en
Open access
Locations
  • Molecular Psychiatry (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
  • HAL (submittedVersion, other-oa)
  • Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
Funders
National Alliance for Research on Schizophrenia and Depression
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
NMDA receptor, parvalbumin interneurons, gamma oscillations, fast-spiking interneurons, NMDA receptor antagonists, cognitive impairment, working memory, associative learning, habituation, stereotypy, psychosis-like symptoms, cortical oscillations, optogenetic stimulation
MeSH terms
Animals, Association Learning, Conditioning, Psychological, Interneurons, Male, Memory, Short-Term, Mice, Transgenic, Parvalbumins, Photic Stimulation, Picrotoxin, Stereotyped Behavior, Receptors, N-Methyl-D-Aspartate, GABA Antagonists, Maze Learning, Excitatory Postsynaptic Potentials, Mice, Sensory Gating, Brain Waves, GABAergic Neurons

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