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Neuronal network activity controls microglial process surveillance in awake mice via norepinephrine signaling

Open access
Liu, Yong U., Ying, Yanlu, Li, Yujiao, Eyo, Ukpong B., Chen, Tingjun, Zheng, Jiaying, Umpierre, Anthony D., Zhu, Jia, Bosco, Dale B., Dong, Hailong, Wu, Long-Jun·2019·Nature Neuroscience

Published version of a preprint

Abstract

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.Liu et al. show that microglial process surveillance is restrained in awake mice, and that reduced neuronal activity due to anesthesia, sensory deprivation or optogenetic inhibition increases microglial dynamics via norepinephrine signaling.

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Show all 22 references

Research works printed but not linked: 30

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Cited by

Metadata

Authors
Liu, Y. U., Ying, Y., Li, Y., Eyo, U. B., Chen, T., Zheng, J., Umpierre, A. D., Zhu, J., Bosco, D. B., Dong, H., & Wu, L.-J.
Venue
Nature Neuroscience
Published
2019-10-21
Volume
22
Issue
11
Pages
1771-1781
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
OpenAlex
W2981347614
Cited by
400
References
22
FWCI
17.67
Type
journal article
Language
en
Open access
green
Licence
Funders
  • U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research (R21DE025689)
  • U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (R01NS112144, R01NS088627)

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