Microglia modulate hippocampal synaptic transmission and sleep duration along the light/dark cycle
Glia. 2021-09-06; 70(1): 89-105
DOI: 10.1002/glia.24090
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Corsi G(1), Picard K(2), di Castro MA(1), Garofalo S(1), Tucci F(1)(3), CheceG(1), Del Percio C(1), Golia MT(1), Raspa M(4), Scavizzi F(4), Decoeur F(5), Lauro C(1), Rigamonti M(6), Iannello F(6), Ragozzino DA(1), Russo E(7), Bernardini G(7), Nadjar A(5)(8), Tremblay ME(2)(9)(10), Babiloni C(1)(3), Maggi L(1), Limatola C(11)(12).
Author information:
(1)Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
(2)Axe Neurosciences, Centre de Recherche du CHU de Québec, Université Laval, Quebec City, Quebec, Canada.
(3)Department of Neurology, San Raffaele of Cassino, Cassino (FR), Italy.
(4)National Research Council, Institute of Biochemistry and Cell Biology (EMMA/Infrafrontier/IMPC, International Campus « A. Buzzati-Traverso », Rome, Italy.
(5)INRAE, Bordeaux INP, NutriNeuro UMR 1286, Bordeaux University, Bordeaux, France.
(6)Tecniplast S.P.A., Buguggiate, Varese, Italy.
(7)Department of Molecular Medicine, Sapienza University, Rome, Italy.
(8)INSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, Bordeaux, France.
(9)Division of Medical Sciences, University of Victoria, Victoria, British Columbia, Canada.
(10)The Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, British Columbia, Canada.
(11)Department of Physiology and Pharmacology, Sapienza University, Laboratory affiliated to Istituto Pasteur Italia, Rome, Italy.
(12)Department of Neurophysiology, Neuropharmacology, Inflammaging, IRCCS Neuromed, Pozzilli, Italy.
Microglia, the brain’s resident macrophages, actively contribute to the homeostasis of cerebral parenchyma by sensing neuronal activity and supporting synaptic remodeling and plasticity. While several studies demonstrated different roles for astrocytes in sleep, the contribution of microglia in the regulation of sleep/wake cycle and in the modulation of synaptic activity in the different day phases has not been deeply investigated. Using light as a zeitgeber cue, we studied the effects of microglial depletion with the colony stimulating factor-1 receptor antagonist PLX5622 on the sleep/wake cycle and on hippocampal synaptictransmission in male mice. Our data demonstrate that almost complete microglial depletion increases the duration of NREM sleep and reduces the hippocampal excitatory neurotransmission. The fractalkine receptor CX3CR1 plays a relevant role in these effects, because cx3cr1GFP/GFP mice recapitulate what found in PLX5622-treated mice. Furthermore, during the light phase, microglia express lower levels of cx3cr1 and a reduction of cx3cr1 expression is also observed when cultured microglial cells are stimulated by ATP, a purinergic molecule released during sleep. Our findings suggest that microglia participate in the regulation of sleep, adapting their cx3cr1 expression in response to the light/dark phase, and modulating synaptic activity in a phase-dependent manner.
© 2021 The Authors. GLIA published by Wiley Periodicals LLC.