Microglia control glutamatergic synapses in the adult mouse hippocampus
Microglia control glutamatergic synapses in the adult mouse hippocampus
ABSTRACT Microglial cells are active players in regulating synaptic development and plasticity in the brain. However, how these cells influence the normal functioning of synapses is largely unknown. In this study, we characterized the effects of pharmacological depletion of microglia, achieved by administration of PLX5622, on hippocampal CA3-CA1 synapses of adult wild type mice. Following microglial depletion, we observed a reduction of spontaneous and evoked glutamatergic activity associated with a decrease of dendritic spine density. We also observed the appearance of immature synaptic features accompanied by higher levels of plasticity. In addition, microglia depleted mice showed a deficit in the acquisition of the Novel Object Recognition task. Remarkably, microglial repopulation after PLX5622 withdrawal was associated with the recovery of hippocampal synapses and learning functions. Altogether, these data demonstrate that microglia contribute to normal synaptic functioning in the adult brain and that their removal induces reversible changes in synaptic organization and activity of glutamatergic synapses.
Tremblay Marie E.、Basilico Bernadette、Reverte Ingrid、Marrone Maria C.、St-Pierre Marie-Kim、Carrier Micael、Renzi Massimiliano、Scavizzi Ferdinando、Marinelli Silvia、Caprioli Daniele、De Turris Valeria、Di Angelantonio Silvia、Garofalo Stefano、Pagani Francesca、Salerno Debora、Golia Maria T.、Maggi Laura、Raspa Marcello、Grimaldi Alfonso、Ragozzino Davide、Limatola Cristina、Rosito Maria、Ferretti Valentina、Ratano Patrizia、Giubettini Maria、Ferrucci Laura、Gross Cornelius T.
Centre de Recherche du CHU de Qu¨|bec, Axe Neurosciences Qu¨|bec D¨|partement de m¨|decine mol¨|culaire, Universit¨| Laval Qu¨|bec||Division of Medical Sciences, University of VictoriaDepartment of Physiology and Pharmacology, Sapienza University of RomeDepartment of Physiology and Pharmacology, Sapienza University of Rome||Santa Lucia Foundation (IRCCS Fondazione Santa Lucia)European Brain Research Institute-Rita Levi MontalciniCentre de Recherche du CHU de Qu¨|bec, Axe Neurosciences Qu¨|bec D¨|partement de m¨|decine mol¨|culaire, Universit¨| Laval Qu¨|becCentre de Recherche du CHU de Qu¨|bec, Axe Neurosciences Qu¨|bec D¨|partement de m¨|decine mol¨|culaire, Universit¨| Laval Qu¨|becDepartment of Physiology and Pharmacology, Sapienza University of RomeNational Research Council, Institute of Biochemistry and Cell Biology (CNR-IBBC/EMMA/Infrafrontier/IMPC), International Campus ?°A. Buzzati-Traverso?±Santa Lucia Foundation (IRCCS Fondazione Santa Lucia)Department of Physiology and Pharmacology, Sapienza University of Rome||Santa Lucia Foundation (IRCCS Fondazione Santa Lucia)Center for Life Nanoscience, Istituto Italiano di TecnologiaDepartment of Physiology and Pharmacology, Sapienza University of Rome||Center for Life Nanoscience, Istituto Italiano di TecnologiaDepartment of Physiology and Pharmacology, Sapienza University of RomeCenter for Life Nanoscience, Istituto Italiano di TecnologiaCenter for Life Nanoscience, Istituto Italiano di TecnologiaDepartment of Physiology and Pharmacology, Sapienza University of RomeDepartment of Physiology and Pharmacology, Sapienza University of RomeNational Research Council, Institute of Biochemistry and Cell Biology (CNR-IBBC/EMMA/Infrafrontier/IMPC), International Campus ?°A. Buzzati-Traverso?±Center for Life Nanoscience, Istituto Italiano di TecnologiaDepartment of Physiology and Pharmacology, Sapienza University of Rome||Santa Lucia Foundation (IRCCS Fondazione Santa Lucia)Department of Physiology and Pharmacology, Sapienza University of Rome||IRCCS NeuromedCenter for Life Nanoscience, Istituto Italiano di TecnologiaDipartimento di Biologia e Biotecnologie ?°Charles Darwin?±, Sapienza University of RomeIRCCS NeuromedCenter for Life Nanoscience, Istituto Italiano di Tecnologia||CrestOptics S.p.A.Department of Physiology and Pharmacology, Sapienza University of RomeEpigenetics and Neurobiology Unit, European Molecular Biology Laboratory (EMBL)
基础医学神经病学、精神病学生物科学研究方法、生物科学研究技术
glutamatergic transmissionhippocampuslearningmicroglianeuron-microglia interaction
Tremblay Marie E.,Basilico Bernadette,Reverte Ingrid,Marrone Maria C.,St-Pierre Marie-Kim,Carrier Micael,Renzi Massimiliano,Scavizzi Ferdinando,Marinelli Silvia,Caprioli Daniele,De Turris Valeria,Di Angelantonio Silvia,Garofalo Stefano,Pagani Francesca,Salerno Debora,Golia Maria T.,Maggi Laura,Raspa Marcello,Grimaldi Alfonso,Ragozzino Davide,Limatola Cristina,Rosito Maria,Ferretti Valentina,Ratano Patrizia,Giubettini Maria,Ferrucci Laura,Gross Cornelius T..Microglia control glutamatergic synapses in the adult mouse hippocampus[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/2021.02.01.429096.点此复制
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