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Temporal Memory and Its Enhancement by Estradiol Requires Surface Dynamics of Hippocampal CA1 N-Methyl-D-Aspartate Receptors

  • Author Footnotes
    1 Authors MP and FG contributed equally to this work.
    Mylène Potier
    Footnotes
    1 Authors MP and FG contributed equally to this work.
    Affiliations
    Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862 l’Institut National de la Santé et de la Recherche Médicale, Bordeaux, France

    Université de Bordeaux (MP, FG, LB-B, LL, VL, SAA, LG), Bordeaux, France
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  • Author Footnotes
    1 Authors MP and FG contributed equally to this work.
    François Georges
    Footnotes
    1 Authors MP and FG contributed equally to this work.
    Affiliations
    Interdisciplinary Institute for NeuroSciences (FG, LL, LG, AM), Centre National de la Recherche Scientifique, Unite Mixte de Recherche 5297, Bordeaux, France

    Université de Bordeaux (MP, FG, LB-B, LL, VL, SAA, LG), Bordeaux, France
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  • Laurent Brayda-Bruno
    Affiliations
    Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862 l’Institut National de la Santé et de la Recherche Médicale, Bordeaux, France

    Université de Bordeaux (MP, FG, LB-B, LL, VL, SAA, LG), Bordeaux, France
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  • Laurent Ladépêche
    Affiliations
    Interdisciplinary Institute for NeuroSciences (FG, LL, LG, AM), Centre National de la Recherche Scientifique, Unite Mixte de Recherche 5297, Bordeaux, France

    Université de Bordeaux (MP, FG, LB-B, LL, VL, SAA, LG), Bordeaux, France
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  • Valérie Lamothe
    Affiliations
    Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862 l’Institut National de la Santé et de la Recherche Médicale, Bordeaux, France

    Université de Bordeaux (MP, FG, LB-B, LL, VL, SAA, LG), Bordeaux, France
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  • Alice Shaam Al Abed
    Affiliations
    Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862 l’Institut National de la Santé et de la Recherche Médicale, Bordeaux, France

    Université de Bordeaux (MP, FG, LB-B, LL, VL, SAA, LG), Bordeaux, France
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  • Author Footnotes
    2 Authors LG and AM are joint senior authors.
    Laurent Groc
    Footnotes
    2 Authors LG and AM are joint senior authors.
    Affiliations
    Interdisciplinary Institute for NeuroSciences (FG, LL, LG, AM), Centre National de la Recherche Scientifique, Unite Mixte de Recherche 5297, Bordeaux, France

    Université de Bordeaux (MP, FG, LB-B, LL, VL, SAA, LG), Bordeaux, France
    Search for articles by this author
  • Author Footnotes
    2 Authors LG and AM are joint senior authors.
    Aline Marighetto
    Correspondence
    Address correspondence to Aline Marighetto, Ph.D., INSERM U862, A. Marighetto, Equipe Physiopathologie de la Mémoire Déclarative, Neurocentre Magendie Unité, 146 rue Léo Saignat, Bordeaux Cedex 33077, France.
    Footnotes
    2 Authors LG and AM are joint senior authors.
    Affiliations
    Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862 l’Institut National de la Santé et de la Recherche Médicale, Bordeaux, France

    Interdisciplinary Institute for NeuroSciences (FG, LL, LG, AM), Centre National de la Recherche Scientifique, Unite Mixte de Recherche 5297, Bordeaux, France
    Search for articles by this author
  • Author Footnotes
    1 Authors MP and FG contributed equally to this work.
    2 Authors LG and AM are joint senior authors.

      Abstract

      Background

      Identifying the underlying cellular mechanisms of episodic memory is an important challenge, since this memory, based on temporal and contextual associations among events, undergoes preferential degradation in aging and various neuropsychiatric disorders. Memory storage of temporal and contextual associations is known to rely on hippocampal N-methyl-D-aspartate receptor (NMDAR)-dependent synaptic plasticity, which depends ex vivo on dynamic organization of surface NMDARs. Whether NMDAR surface trafficking sustains the formation of associative memory, however, remains unknown.

      Methods

      We tested this hypothesis, using single nanoparticle imaging, electrophysiology, and behavioral approaches, in hippocampal networks challenged with a potent modulator of NMDAR-dependent synaptic plasticity and memory, 17β-estradiol (E2).

      Results

      We demonstrate that E2 modulates NMDAR surface trafficking, a necessary condition for E2-induced potentiation at hippocampal cornu ammonis 1 synapses. Strikingly, cornu ammonis 1 NMDAR surface trafficking controls basal and E2-enhanced mnemonic retention of temporal, but not contextual, associations.

      Conclusions

      NMDAR surface trafficking and its modulation by the sex hormone E2 is a cellular mechanism critical for a major component of episodic memory, opening a new and noncanonical research avenue in the physiopathology of cognition.

      Keywords

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