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Dendritic NMDA receptors in parvalbumin neurons enable strong and stable neuronal assemblies

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Cite this article as: eLife 2019;8:e49872 doi: 10.7554/eLife.49872

Abstract

Parvalbumin-expressing (PV+) GABAergic interneurons mediate feedforward and feedback inhibition and have a key role in gamma oscillations and information processing. The importance of fast synaptic recruitment, action potential initiation and repolarization, and rapid synchronous GABA release by PV+ cells is well established. In contrast, the functional significance of PV+ cell NMDA receptors (NMDARs), which generate relatively slow postsynaptic currents, is unclear. Underlining their importance, several studies implicate PV+ cell NMDAR disruption in impaired network function and circuit pathologies. Here, we show that dendritic NMDARs underlie supralinear integration of feedback excitation from local pyramidal neurons onto mouse CA1 PV+ cells. Furthermore, by incorporating NMDARs at feedback connections onto PV+ cells in spiking networks, we show that these receptors enable cooperative recruitment of PV+ interneurons, strengthening and stabilising principal cell assemblies. Failure of this phenomenon provides a parsimonious explanation for cognitive and sensory gating deficits in pathologies with impaired PV+ NMDAR signalling.

Article and author information

Author details

  1. Jonathan H Cornford

    UCL Institute of Neurology, University College London, London, United Kingdom
    For correspondence
    jonathan.cornford.12@ucl.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
  2. Marion S Mercier

    UCL Institute of Neurology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3929-8118
  3. Marco Leite

    UCL Institute of Neurology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Vincent Magloire

    UCL Institute of Neurology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Michael Häusser

    Wolfson Institute for Biomedical Research, Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Dimitri Michael Kullmann

    UCL Institute of Neurology, University College London, London, United Kingdom
    For correspondence
    d.kullmann@ucl.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6696-3545

Funding

Wellcome (095580/Z/11/Z)

  • Jonathan H Cornford
  • Marion S Mercier
  • Marco Leite
  • Vincent Magloire
  • Dimitri Michael Kullmann

Wellcome (212285/Z/18/Z)

  • Dimitri Michael Kullmann

Medical Research Council (MR/L01095X/1)

  • Vincent Magloire

Brain Research Trust

  • Jonathan H Cornford

Wellcome

  • Michael Häusser

Epilepsy Research UK (P1702)

  • Vincent Magloire

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: The study was performed in accordance with the Animals (Scientific Procedures) Act 1986 and reviewed by the Animal Welfare and Ethical Review Body (AWERB) of the UCL Queen Square Institute of Neurology.

Reviewing Editor

  1. Marlene Bartos, University of Freiburg, Germany

Publication history

  1. Received: July 3, 2019
  2. Accepted: October 26, 2019
  3. Accepted Manuscript published: October 28, 2019 (version 1)
  4. Version of Record published: November 8, 2019 (version 2)

Copyright

© 2019, Cornford et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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