TY - JOUR
T1 - Microglia control glutamatergic synapses in the adult mouse hippocampus
AU - Basilico, Bernadette
AU - Ferrucci, Laura
AU - Ratano, Patrizia
AU - Golia, Maria T
AU - Grimaldi, Alfonso
AU - Rosito, Maria
AU - Ferretti, Valentina
AU - Reverte, Ingrid
AU - Sanchini, Caterina
AU - Marrone, Maria C
AU - Giubettini, Maria
AU - De Turris, Valeria
AU - Salerno, Debora
AU - Garofalo, Stefano
AU - St-Pierre, Marie-Kim
AU - Carrier, Micael
AU - Renzi, Massimiliano
AU - Pagani, Francesca
AU - Modi, Brijesh
AU - Raspa, Marcello
AU - Scavizzi, Ferdinando
AU - Gross, Cornelius T
AU - Marinelli, Silvia
AU - Tremblay, Marie-Ève
AU - Caprioli, Daniele
AU - Maggi, Laura
AU - Limatola, Cristina
AU - Di Angelantonio, Silvia
AU - Ragozzino, Davide
N1 - © 2021 The Authors. GLIA published by Wiley Periodicals LLC.
PY - 2022/1
Y1 - 2022/1
N2 - Microglia 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 ofneuroinflammatory 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.
AB - Microglia 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 ofneuroinflammatory 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.
U2 - 10.1002/glia.24101
DO - 10.1002/glia.24101
M3 - Article
C2 - 34661306
SN - 0894-1491
VL - 70
SP - 173
EP - 195
JO - GLIA
JF - GLIA
IS - 1
ER -