GluN2D-mediated excitatory drive onto medial prefrontal cortical PV+ fast-spiking inhibitory interneurons.

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  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science
    • Subject Terms:
      Interneurons/*metabolism ; Parvalbumins/*metabolism ; Prefrontal Cortex/*physiology ; Receptors, N-Methyl-D-Aspartate/*metabolism; Action Potentials ; Adult ; Animals ; Female ; Gene Expression ; Humans ; Male ; Mice, Inbred C57BL ; Middle Aged ; Neural Inhibition ; Pyramidal Cells/metabolism ; RNA, Messenger/genetics ; Receptors, N-Methyl-D-Aspartate/genetics
    • Abstract:
      Deficits in fast-spiking inhibitory interneurons (FSINs) within the dorsolateral prefrontal cortex (dlPFC) are hypothesized to underlie cognitive impairment associated with schizophrenia. Though representing a minority of interneurons, this key cell type coordinates broad neural network gamma-frequency oscillations, associated with cognition and cognitive flexibility. Here we report expression of GluN2D mRNA selectively in parvalbumin positive cells of human postmortem dlPFC tissue, but not pyramidal neurons, with little to no GluN2C expression in either cell type. In acute murine mPFC slices the GluN2C/D selective positive allosteric modulator (PAM), CIQ(+), increased the intrinsic excitability as well as enhanced NMDAR-mediated EPSCs onto FSINs. This increase in intrinsic excitability with GluN2C/D PAM was also observed in the Dlx 5/6+/- FSIN developmental deficit model with reported FSIN hypoexcitability. Together these data speak to selective modulation of FSINs by a GluN2D PAM, providing a potential mechanism to counter the FSIN-deficit seen in schizophrenia.
      Competing Interests: Numerous contributing authors had at the time of the study and continue to have commercial affiliations. However the funds from Pfizer Neuroscience covered salaries and materials, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript beyond supporting the listed authors’ salaries (Funding Statement), materials, and the dissemination costs (commitment to cover submission fees). Commercial affiliations in no way have impacted our adherence to PLOS ONE policies on sharing data and materials.
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    • Grant Information:
      R01 MH106507 United States MH NIMH NIH HHS
    • Accession Number:
      0 (NR2D NMDA receptor)
      0 (Parvalbumins)
      0 (RNA, Messenger)
      0 (Receptors, N-Methyl-D-Aspartate)
    • Publication Date:
      Date Created: 20200605 Date Completed: 20200821 Latest Revision: 20200821
    • Publication Date:
      20240104
    • Accession Number:
      PMC7272025
    • Accession Number:
      10.1371/journal.pone.0233895
    • Accession Number:
      32497062