biostudies-literatureLiu YUNIDCR NIH HHSU.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial ResearchU.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and StrokeNINDS NIH HHS1771-1781https://www.ebi.ac.uk/biostudies/studies/S-EPMC6858573biostudies-literatureUnknown22(11)Microglia dynamically survey the brain parenchyma. Microglial processes interact with neuronal elements; however, what role neuronal network activity plays in regulating microglial dynamics is not entirely clear. Most studies of microglial dynamics use either slice preparations or in vivo imaging in anesthetized mice. Here we demonstrate that microglia in awake mice have a relatively reduced process area and surveillance territory and that reduced neuronal activity under general anesthesia increases microglial process velocity, extension and territory surveillance. Similarly, reductions in local neuronal activity through sensory deprivation or optogenetic inhibition increase microglial process surveillance. Using pharmacological and chemogenetic approaches, we demonstrate that reduced norepinephrine signaling is necessary for these increases in microglial process surveillance. These findings indicate that under basal physiological conditions, noradrenergic tone in awake mice suppresses microglial process surveillance. Our results emphasize the importance of awake imaging for studying microglia-neuron interactions and demonstrate how neuronal activity influences microglial process dynamics.Nature neuroscienceNeuronal network activity controls microglial process surveillance in awake mice via norepinephrine signaling.PMC6858573R01 NS088627R21DE025689F32 NS114040R21 DE025689R01NS088627R01 NS112144R01NS112144Zheng JUmpierre ADLi YZhu JDong HYing YEyo UBBosco DBLiu YUChen TWu LJfalseNeuronal network activity controls microglial process surveillance in awake mice via norepinephrine signaling.Microglia dynamically survey the brain parenchyma. Microglial processes interact with neuronal elements; however, what role neuronal network activity plays in regulating microglial dynamics is not entirely clear. Most studies of microglial dynamics use either slice preparations or in vivo imaging in anesthetized mice. Here we demonstrate that microglia in awake mice have a relatively reduced process area and surveillance territory and that reduced neuronal activity under general anesthesia increases microglial process velocity, extension and territory surveillance. Similarly, reductions in local neuronal activity through sensory deprivation or optogenetic inhibition increase microglial process surveillance. Using pharmacological and chemogenetic approaches, we demonstrate that reduced norepinephrine signaling is necessary for these increases in microglial process surveillance. These findings indicate that under basal physiological conditions, noradrenergic tone in awake mice suppresses microglial process surveillance. Our results emphasize the importance of awake imaging for studying microglia-neuron interactions and demonstrate how neuronal activity influences microglial process dynamics.2019-01-01T00:00:00Z2019 Nov2024-12-03T21:13:19.758Z2020-05-22T17:30:24ZS-EPMC68585733163644910.1038/s41593-019-0511-3