Microglia, the brain's resident macrophages, actively contributes 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 synaptic transmission 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.

Microglia modulates hippocampal synaptic transmission and sleep duration along the light/dark cycle / Corsi, G.; Picard, K.; di Castro, M. A.; Garofalo, S.; Tucci, F.; Chece, G.; del Percio, C.; Golia, M. T.; Raspa, M.; Scavizzi, F.; Decoeur, F.; Lauro, C.; Rigamonti, M.; Iannello, F.; Ragozzino, D. A.; Russo, E.; Bernardini, G.; Nadjar, A.; Tremblay, M. E.; Babiloni, C.; Maggi, L.; Limatola, C.. - In: GLIA. - ISSN 0894-1491. - (2022), pp. 1-17. [10.1002/glia.24090]

Microglia modulates hippocampal synaptic transmission and sleep duration along the light/dark cycle

Corsi G.;di Castro M. A.;Garofalo S.
;
Tucci F.;Chece G.;del Percio C.;Golia M. T.;Lauro C.;Iannello F.;Ragozzino D. A.;Russo E.;Bernardini G.;Babiloni C.;Maggi L.;Limatola C.
2022

Abstract

Microglia, the brain's resident macrophages, actively contributes 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 synaptic transmission 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.
2022
cx3cr1; electroencephalography; long-term potentiation; microglial depletion; miniature excitatory post-synaptic currents; sleep; spontaneous excitatory post-synaptic currents
01 Pubblicazione su rivista::01a Articolo in rivista
Microglia modulates hippocampal synaptic transmission and sleep duration along the light/dark cycle / Corsi, G.; Picard, K.; di Castro, M. A.; Garofalo, S.; Tucci, F.; Chece, G.; del Percio, C.; Golia, M. T.; Raspa, M.; Scavizzi, F.; Decoeur, F.; Lauro, C.; Rigamonti, M.; Iannello, F.; Ragozzino, D. A.; Russo, E.; Bernardini, G.; Nadjar, A.; Tremblay, M. E.; Babiloni, C.; Maggi, L.; Limatola, C.. - In: GLIA. - ISSN 0894-1491. - (2022), pp. 1-17. [10.1002/glia.24090]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1571160
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