Plasticity of NMDA Receptor Expression During Mouse Cerebellar Granule Cell Development

Authors

  • Michel Didier,

    Corresponding author
    1. 1SANOFI Recherche, Neuropsychiatry Department, 371 rue du Prof. J. Blayac, 34184 Montpellier cedex 04, France
    2. 2Harvard Medical School, Laboratories for Molecular Neuroscience, McLean Hospital, 115 Mill Street, Belmont, MA 02178, USA
      Correspondence to: Michel Didier, Harvard Medical School, Laboratories for Molecular Neuroscience, McLean Hospital, 115 Mill Street, Belmont, MA 02178, USA
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  • Jean-Marc Mienville,

    1. 1SANOFI Recherche, Neuropsychiatry Department, 371 rue du Prof. J. Blayac, 34184 Montpellier cedex 04, France
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    • 4

      Laboratory of Neurophysiology, National Institute of Neuronal Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA

  • Philippe Soubrié,

    1. 1SANOFI Recherche, Neuropsychiatry Department, 371 rue du Prof. J. Blayac, 34184 Montpellier cedex 04, France
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  • Joël Bockaert,

    1. 1SANOFI Recherche, Neuropsychiatry Department, 371 rue du Prof. J. Blayac, 34184 Montpellier cedex 04, France
    2. 3CNRS/UPR9023, CCIPE, rue de la Cardonille, 34094 Montpellier cedex 05, France
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  • Stephen Berman,

    1. 2Harvard Medical School, Laboratories for Molecular Neuroscience, McLean Hospital, 115 Mill Street, Belmont, MA 02178, USA
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  • Sherry Bursztajn,

    1. 2Harvard Medical School, Laboratories for Molecular Neuroscience, McLean Hospital, 115 Mill Street, Belmont, MA 02178, USA
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  • Jean-Philippe Pin

    1. 1SANOFI Recherche, Neuropsychiatry Department, 371 rue du Prof. J. Blayac, 34184 Montpellier cedex 04, France
    2. 3CNRS/UPR9023, CCIPE, rue de la Cardonille, 34094 Montpellier cedex 05, France
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Correspondence to: Michel Didier, Harvard Medical School, Laboratories for Molecular Neuroscience, McLean Hospital, 115 Mill Street, Belmont, MA 02178, USA

Abstract

A period of hypersensitivity to N-methyl-d-aspartate (NMDA) has been described during the early development of different types of neuron. Since activation of NMDA receptors can also induce rapid neuron death, the hypersensitivity to NMDA may be tightly controlled. In the present study we show that mouse cerebellar granule neurons become transiently hypersensitive to NMDA between days 10 and 14 after plating in a culture medium containing 30 mM K+. The NMDA sensitivity is higher when cells are cultured in the presence of an NMDA receptor antagonist [30 mM K+ plus 100 μM 3-((±)-2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP)], and no hypersensitivity is observed when cells are cultured in the continuous presence of NMDA (12.5 mM K+ plus 100 μM NMDA). The high NMDA sensitivity in control cells is associated with a higher density of NMDA receptors than that measured in NMDA-treated cells, suggesting that the sensitivity to NMDA may be partly controlled by activity-dependent NMDA receptor down-regulation. We also examined the level of NMDA-ζ1 mRNA and found no correlation between this parameter and the transient pattern of NMDA sensitivity. Such NMDA receptor plasticity may be of importance in the central nervous system, protecting developing cells from excitotoxicity at critical developmental stages.

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