期刊
JOURNAL OF NEUROSCIENCE
卷 41, 期 6, 页码 1274-1287出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2140-20.2020
关键词
excitatory; perineuronal nets; plasticity; parvalbumin; synaptic connections; visual cortex
资金
- National Institutes of Health (National Institute of Neurological Disorders and Stroke) [1R01NS083801]
- National Institutes of Health (National Institute on Aging) [RF1AG056768, R01EY028212, R35GM127102]
Microglia play a crucial role in sculpting neuronal circuit connectivity and regulating subsequent functional activity in the adult cortex. Depletion of microglia increases synaptic connections and enhances neural activities, which recover following re-population of adult microglia.
Microglia have crucial roles in sculpting synapses and maintaining neural circuits during development. To test the hypothesis that microglia continue to regulate neural circuit connectivity in adult brain, we have investigated the effects of chronic microglial depletion, via CSF1R inhibition, on synaptic connectivity in the visual cortex in adult mice of both sexes. We find that the absence of microglia dramatically increases both excitatory and inhibitory synaptic connections to excitatory cortical neurons assessed with functional circuit mapping experiments in acutely prepared adult brain slices. Microglia depletion leads to increased densities and intensities of perineuronal nets. Furthermore, in vivo calcium imaging across large populations of visual cortical neurons reveals enhanced neural activities of both excitatory neurons and parvalbumin-expressing interneurons in the visual cortex following microglia depletion. These changes recover following adult microglia repopulation. In summary, our new results demonstrate a prominent role of microglia in sculpting neuronal circuit connectivity and regulating subsequent functional activity in adult cortex.
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