Microglia control glutamatergic synapses in the adult mouse hippocampus

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dc.contributor.authorBasilico, Bernadette
dc.contributor.authorFerrucci, Laura
dc.contributor.authorRatano, Patrizia
dc.contributor.authorGolia, Maria T.
dc.contributor.authorGrimaldi, Alfonso
dc.contributor.authorRosito, Maria
dc.contributor.authorFerretti, Valentina
dc.contributor.authorReverte, Ingrid
dc.contributor.authorSanchini, Caterina
dc.contributor.authorMarrone, Maria C.
dc.contributor.authorGiubettini, Maria
dc.contributor.authorDe Turris, Valeria
dc.contributor.authorSalerno, Debora
dc.contributor.authorGarofalo, Stefano
dc.contributor.authorSt-Pierre, Marie-Kim
dc.contributor.authorCarrier, Micael
dc.contributor.authorRenzi, Massimiliano
dc.contributor.authorPagani, Francesca
dc.contributor.authorModi, Brijesh
dc.contributor.authorTremblay, Marie-Ève
dc.contributor.authorCaprioli, Daniele
dc.contributor.authorMaggi, Laura
dc.contributor.authorLimatola, Cristina
dc.contributor.authorDi Angelantonio, Silvia
dc.contributor.authorRagozzino, Davide
dc.date.accessioned2024-02-06T22:19:13Z
dc.date.available2024-02-06T22:19:13Z
dc.date.copyright2022en_US
dc.date.issued2022
dc.descriptionThe authors thank Alessandro Felici, Claudia Valeri, Arsenio Armagno, and Senthilkumar Deivasigamani for help with animal husbandry and transgenic colonies management. They also wish to thank Piotr Bregestovski and Michal Schwartz for helpful discussions and criticism. PLX5622 was provided under Materials Transfer Agreement by Plexxikon Inc. (Berkeley, CA).en_US
dc.description.abstractMicroglia cells are active players in regulating synaptic development and plasticity in the brain. However, how they influence the normal functioning of synapses is largely unknown. In this study, we characterized the effects of pharmacological microglia depletion, 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 and higher levels of plasticity. Microglia depleted mice showed a deficit in the acquisition of the Novel Object Recognition task. These events were accompanied by hippocampal astrogliosis, although in the absence of neuroinflammatory condition. PLX-induced synaptic changes were absent in Cx3cr1 / mice, highlighting the role of CX3CL1/CX3CR1 axis in microglia control of synaptic functioning. Remarkably, microglia 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 organization and activity of glutamatergic synapses.en_US
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipThe work was supported by a grant fromMIUR (PRIN 2017HPTFFC_003) to Davide Ragozzino and in part by funds to Silvia Di Angelantonio (CrestOptics-IIT JointLab for Advanced Microscopy) and Daniele Caprioli (Istituto Pasteur-Fondazione Cenci Bolognetti). Bernadette Basilico, and Laura Ferrucci were supported by the PhD program in Clinical-Experimental Neuroscience and Psychiatry, Sapienza University, Rome; Caterina Sanchini was supported by the PhD program in Life Science, Sapienza University, Rome and by the Italian Institute of Technology, Rome. Open Access Funding provided by Universita degli Studi di Roma La Sapienza within the CRUI-CARE Agreement.en_US
dc.identifier.citationBasilico, B., Ferrucci, L., Ratano, P., Golia, M. T., Grimaldi, A., Rosito, M., ... Ragozzino, D. (2022). Microglia control glutamatergic synapses in the adult mouse hippocampus. Glia, 70(1), 173-195. https://doi.org/10.1002/glia.24101en_US
dc.identifier.urihttps://doi.org/10.1002/glia.24101
dc.identifier.urihttp://hdl.handle.net/1828/15953
dc.language.isoenen_US
dc.publisherGliaen_US
dc.subjectglutamatergic transmission
dc.subjecthippocampus
dc.subjectlearning
dc.subjectmicroglia
dc.subjectneuron-microglia interaction
dc.subjectsynapses
dc.subject.departmentDivision of Medical Sciences
dc.subject.departmentSchool of Medical Sciences
dc.titleMicroglia control glutamatergic synapses in the adult mouse hippocampusen_US
dc.typeArticleen_US

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