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Physiological synaptic activity and recognition memory require astroglial glutamine

Nature Communications, vol. 13, pp. 753

Abstract

Presynaptic glutamate replenishment is fundamental to brain function. In high activity regimes, such as epileptic episodes, this process is thought to rely on the glutamate-glutamine cycle between neurons and astrocytes. However the presence of an astroglial glutamine supply, as well as its functional relevance in vivo in the healthy brain remain controversial, partly due to a lack of tools that can directly examine glutamine transfer. Here, we generated a fluorescent probe that tracks glutamine in live cells, which provides direct visual evidence of an activity-dependent glutamine supply from astroglial networks to presynaptic structures under physiological conditions. This mobilization is mediated by connexin43, an astroglial protein with both gap-junction and hemichannel functions, and is essential for synaptic transmission and object recognition memory. Our findings uncover an indispensable recruitment of astroglial glutamine in physiological synaptic activity and memory via an unconventional pathway, thus providing an astrocyte basis for cognitive processes.

Authors 15

  1. Centre National de la Recherche Scientifique · Inserm · Institute of Science and Technology Austria · Collège de France · Université Paris Sciences et Lettres · Centre Interdisciplinaire de Recherche en Biologie

    Affiliation as printed

    Institute of Science and Technology Austria, Klosterneuburg, Austria

    Neuroglial Interactions in Cerebral Physiology and Pathologies, Center for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS, INSERM, Labex Memolife, Université PSL, Paris, France

  2. Centre National de la Recherche Scientifique · Inserm · Collège de France · Université Paris Sciences et Lettres · University of Belgrade · Centre Interdisciplinaire de Recherche en Biologie

    Affiliation as printed

    Institute for Physiology and Biochemistry Ivan Djaja, Faculty of Biology, University of Belgrade, Belgrade, Serbia

    Neuroglial Interactions in Cerebral Physiology and Pathologies, Center for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS, INSERM, Labex Memolife, Université PSL, Paris, France

  3. Centre National de la Recherche Scientifique · Inserm · Collège de France · Université Paris Sciences et Lettres · Centre Interdisciplinaire de Recherche en Biologie · Université Pierre-et-Marie-Curie

    Affiliation as printed

    Doctoral School N°158, Pierre and Marie Curie University, Paris, France

    Neuroglial Interactions in Cerebral Physiology and Pathologies, Center for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS, INSERM, Labex Memolife, Université PSL, Paris, France

  4. Centre National de la Recherche Scientifique · Université Paris-Saclay

    Affiliation as printed

    Université Paris Saclay, ENS Paris-Saclay, CNRS, PPSM, 91190, Gif-sur-Yvette, France

  5. Centre National de la Recherche Scientifique · Inserm · Collège de France · Université Paris Sciences et Lettres · Centre Interdisciplinaire de Recherche en Biologie · Université Pierre-et-Marie-Curie

    Affiliation as printed

    Doctoral School N°158, Pierre and Marie Curie University, Paris, France

    Neuroglial Interactions in Cerebral Physiology and Pathologies, Center for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS, INSERM, Labex Memolife, Université PSL, Paris, France

  6. Centre National de la Recherche Scientifique · Inserm · Collège de France · Université Paris Sciences et Lettres · Université Paris-Saclay · Institut des Neurosciences Paris-Saclay · Centre Interdisciplinaire de Recherche en Biologie

    Affiliation as printed

    Neuroglial Interactions in Cerebral Physiology and Pathologies, Center for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS, INSERM, Labex Memolife, Université PSL, Paris, France

    Université Paris-Saclay, CNRS, Institut des Neurosciences Paris-Saclay, Gif-sur-Yvette, France

  7. Centre National de la Recherche Scientifique · Inserm · Collège de France · Université Paris Sciences et Lettres · Centre Interdisciplinaire de Recherche en Biologie · Université Pierre-et-Marie-Curie

    Affiliation as printed

    Doctoral School N°158, Pierre and Marie Curie University, Paris, France

    Neuroglial Interactions in Cerebral Physiology and Pathologies, Center for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS, INSERM, Labex Memolife, Université PSL, Paris, France

  8. Forschungszentrum Jülich · RWTH Aachen University

    Affiliation as printed

    Department of Psychiatry, Psychotherapy and Psychosomatics, Rheinisch-Westfaelische Technische Hochschule Aachen University, Aachen, Germany

    Institute for Neuroscience and Medicine INM-10, Research Center Jülich, Jülich, Germany

  9. Centre National de la Recherche Scientifique · Inserm · Collège de France · Université Paris Sciences et Lettres · Centre Interdisciplinaire de Recherche en Biologie

    Affiliation as printed

    Neuroglial Interactions in Cerebral Physiology and Pathologies, Center for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS, INSERM, Labex Memolife, Université PSL, Paris, France

  10. Centre National de la Recherche Scientifique · Université Paris-Saclay

    Affiliation as printed

    Université Paris Saclay, ENS Paris-Saclay, CNRS, PPSM, 91190, Gif-sur-Yvette, France

  11. Centre National de la Recherche Scientifique · Inserm · Collège de France · Université Paris Sciences et Lettres · Différenciation et Communication Neuronale et Neuroendocrine · Centre Interdisciplinaire de Recherche en Biologie · Université de Rouen Normandie

    Affiliation as printed

    Neuroglial Interactions in Cerebral Physiology and Pathologies, Center for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS, INSERM, Labex Memolife, Université PSL, Paris, France

    Normandy University, UNIROUEN, INSERM, DC2N, 76000, Rouen, France

  12. Université Paris-Sud · Centre National de la Recherche Scientifique · Commissariat à l'Énergie Atomique et aux Énergies Alternatives · Institut d'Imagerie Biomédicale · Laboratoire des Maladies Neurodégénératives · Molecular Imaging Research Center · Institut de biologie François Jacob

    Affiliation as printed

    Commissariat à l'Energie Atomique et aux Energies Alternatives, Département de la Recherche Fondamentale, Institut de biologie François Jacob, Molecular Imaging Research Center and CNRS UMR9199, Université Paris-Sud, Neurodegenerative Diseases Laboratory, Fontenay-aux-Roses, France

  13. Forschungszentrum Jülich · Jülich Aachen Research Alliance · RWTH Aachen University

    Affiliation as printed

    Department of Psychiatry, Psychotherapy and Psychosomatics, Rheinisch-Westfaelische Technische Hochschule Aachen University, Aachen, Germany

    Institute for Neuroscience and Medicine INM-10, Research Center Jülich, Jülich, Germany

    Jülich-Aachen Research Alliance Translational Brain Medicine, Aachen, Germany

  14. Centre National de la Recherche Scientifique · Université Paris-Saclay

    Affiliation as printed

    Université Paris Saclay, ENS Paris-Saclay, CNRS, PPSM, 91190, Gif-sur-Yvette, France

  15. Nathalie Rouach corresponding

    Centre National de la Recherche Scientifique · Inserm · Collège de France · Université Paris Sciences et Lettres · Centre Interdisciplinaire de Recherche en Biologie

    Affiliation as printed

    Neuroglial Interactions in Cerebral Physiology and Pathologies, Center for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS, INSERM, Labex Memolife, Université PSL, Paris, France. nathalie.rouach@college-de-france.fr

    Neuroglial Interactions in Cerebral Physiology and Pathologies, Center for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS, INSERM, Labex Memolife, Université PSL, Paris, France

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References 72