Physiological synaptic activity and recognition memory are fueled by astroglial glutamine
bioRxiv (Cold Spring Harbor Laboratory)
Abstract
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 novel fluorescent probe that tracks glutamine in live cells, which provided 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 13
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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, Center for Interdisciplinary Research in Biology, Collège de France, CNRS UMR 7241, INSERM U1050, Labex Memolife, PSL Research University Paris, France
Neuroglial Interactions in Cerebral Physiology, Center for Interdisciplinary Research in Biology, Collège de France, CNRS UMR 724, INSERM U050, Labex Memolife, PSL Research University Paris, France
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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, Center for Interdisciplinary Research in Biology, Collège de France, CNRS UMR 7241, INSERM U1050, Labex Memolife, PSL Research University Paris, France
Neuroglial Interactions in Cerebral Physiology, Center for Interdisciplinary Research in Biology, Collège de France, CNRS UMR 724, INSERM U050, Labex Memolife, PSL Research University Paris, France
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Centre National de la Recherche Scientifique · Université Paris-Saclay · École Normale Supérieure - PSL · Laboratoire de Photophysique et Photochimie Supramoléculaires et Macromoléculaires
Affiliation as printed
Laboratoire PPSM, ENS Paris Saclay, CNRS UMR 8531, Université Paris Saclay
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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, Center for Interdisciplinary Research in Biology, Collège de France, CNRS UMR 7241, INSERM U1050, Labex Memolife, PSL Research University Paris, France
Neuroglial Interactions in Cerebral Physiology, Center for Interdisciplinary Research in Biology, Collège de France, CNRS UMR 724, INSERM U050, Labex Memolife, PSL Research University Paris, France
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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, Center for Interdisciplinary Research in Biology, Collège de France, CNRS UMR 7241, INSERM U1050, Labex Memolife, PSL Research University Paris, France
Neuroglial Interactions in Cerebral Physiology, Center for Interdisciplinary Research in Biology, Collège de France, CNRS UMR 724, INSERM U050, Labex Memolife, PSL Research University Paris, France
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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, Center for Interdisciplinary Research in Biology, Collège de France, CNRS UMR 7241, INSERM U1050, Labex Memolife, PSL Research University Paris, France
Neuroglial Interactions in Cerebral Physiology, Center for Interdisciplinary Research in Biology, Collège de France, CNRS UMR 724, INSERM U050, Labex Memolife, PSL Research University Paris, France
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Forschungszentrum Jülich · RWTH Aachen University
Affiliation as printed
Department of Psychiatry, Psychotherapy and Psychosomatics, Rheinisch-Westfaelische Technische Hochschule Aachen University
Institute for Neuroscience and Medicine INM-10, Research Center Jülich, Jülich, Germany
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Centre National de la Recherche Scientifique · Université Paris-Saclay · École Normale Supérieure - PSL · Laboratoire de Photophysique et Photochimie Supramoléculaires et Macromoléculaires
Affiliation as printed
Laboratoire PPSM, ENS Paris Saclay, CNRS UMR 8531, Université Paris Saclay
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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, Center for Interdisciplinary Research in Biology, Collège de France, CNRS UMR 7241, INSERM U1050, Labex Memolife, PSL Research University Paris, France
Neuroglial Interactions in Cerebral Physiology, Center for Interdisciplinary Research in Biology, Collège de France, CNRS UMR 724, INSERM U050, Labex Memolife, PSL Research University Paris, France
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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
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Forschungszentrum Jülich · Jülich Aachen Research Alliance · RWTH Aachen University
Affiliation as printed
Department of Psychiatry, Psychotherapy and Psychosomatics, Rheinisch-Westfaelische Technische Hochschule Aachen University
Institute for Neuroscience and Medicine INM-10, Research Center Jülich, Jülich, Germany
Jülich-Aachen Research Alliance Translational Brain Medicine, Aachen, Germany
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Centre National de la Recherche Scientifique · Université Paris-Saclay · École Normale Supérieure - PSL · Laboratoire de Photophysique et Photochimie Supramoléculaires et Macromoléculaires
Affiliation as printed
Laboratoire PPSM, ENS Paris Saclay, CNRS UMR 8531, Université Paris Saclay
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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, Center for Interdisciplinary Research in Biology, Collège de France, CNRS UMR 7241, INSERM U1050, Labex Memolife, PSL Research University Paris, France
Neuroglial Interactions in Cerebral Physiology, Center for Interdisciplinary Research in Biology, Collège de France, CNRS UMR 724, INSERM U050, Labex Memolife, PSL Research University Paris, France
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