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Noradrenergic signaling in the wakeful state inhibits microglial surveillance and synaptic plasticity in the mouse visual cortex

Stowell, Rianne D ; Sipe, Grayson O ; Dawes, Ryan P ; Batchelor, Hanna N ; Lordy, Katheryn A ; Whitelaw, Brendan S ; Stoessel, Mark B ; Bidlack, Jean M ; Brown, Edward ; Sur, Mriganka ; Majewska, Ania K

Nature neuroscience, 2019-11, Vol.22 (11), p.1782-1792 [Revista revisada por pares]

United States: Nature Publishing Group

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Noradrenergic signaling in the wakeful state inhibits microglial surveillance and synaptic plasticity in the mouse visual cortex
Autor: Stowell, Rianne D ; Sipe, Grayson O ; Dawes, Ryan P ; Batchelor, Hanna N ; Lordy, Katheryn A ; Whitelaw, Brendan S ; Stoessel, Mark B ; Bidlack, Jean M ; Brown, Edward ; Sur, Mriganka ; Majewska, Ania K
Materias: Adrenergic receptors ; Analysis ; Animals ; Arousal ; Benzylamines - pharmacology ; Brain ; Cell Movement - drug effects ; Cell Movement - physiology ; Circadian Rhythm - physiology ; Clenbuterol - pharmacology ; CX3C Chemokine Receptor 1 - genetics ; Dexmedetomidine - pharmacology ; Dominance, Ocular ; Female ; Fentanyl - pharmacology ; Health aspects ; Homeostasis ; Immune system ; Influence ; Injury prevention ; Locus Coeruleus - drug effects ; Male ; Mice ; Mice, Transgenic ; Microglia ; Microglia - cytology ; Microglia - drug effects ; Microglia - physiology ; Nadolol - pharmacology ; Neuronal Plasticity - drug effects ; Neuronal Plasticity - physiology ; Neurons - metabolism ; Neurons - physiology ; Neuroplasticity ; Noradrenaline ; Norepinephrine ; Norepinephrine - metabolism ; Norepinephrine - physiology ; Parenchyma ; Plasticity ; Propanolamines - pharmacology ; Psychological aspects ; Receptor mechanisms ; Receptors ; Receptors (physiology) ; Restraint, Physical - physiology ; Signaling ; Surveillance ; Synaptic plasticity ; Terbutaline - pharmacology ; Variation ; Visual cortex ; Visual Cortex - physiology ; Visual plasticity ; Wakefulness ; Wounds and Injuries - physiopathology
Es parte de: Nature neuroscience, 2019-11, Vol.22 (11), p.1782-1792
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SourceType-Scholarly Journals-1
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R.D.S, G.O.S, and A.K.M conceived the project. R.D.S, G.O.S, R.P.D, H.N.B, K.A.L., B.S.W, and M.B.S. carried out experiments and data analysis. R.D.S carried out iOS imaging experiments and analysis in Cx3cr1CreERT/β2fl/fl, Cx3cr1CreERT, C57BL6J mice, and all in vivo two-photon experiments characterizing awake v. anesthetized mice, adrenergic pharmacological agents and imaging experiments utilizing Cx3cr1CreERT/β2fl/fl/Ai9, Cx3cr1CreERT/Ai9 mice. R.D.S also performed all FACS preparation on microglial specimens. G.O.S carried out iOS imaging experiments in C57BL6J mice and imaging experiments characterizing stress and circadian rhythms. G.O.S also performed experiments utilizing terbutaline. G.O.S performed all resonance imaging and optogenetic experiments. R.P.D carried out stress experiments. H.N.B assisted in confirmation of Cx3cr1Cre/β2fl/fl excision and DSP4 depletion histology experiments. K.A.L carried out circadian morphology experiments. B.S.W performed all slice experiments. M.B.S. assisted with DSP4 histology experiments, and Cx3cr1Cre/β2fl/fl expression histology. J.M.B contributed to experimental design of experiments with pharmacological agents. E.B. advised on experimental design and analysis of stress experiments. M.S. advised on experimental design and analysis of optogenetic and resonance imaging experiments. R.D.S, G.O.S, and A.K.M wrote the first draft of the manuscript. All authors contributed to the final version of the manuscript.
These authors contributed equally to this work.
Author Contributions
Descripción: Microglia are the brain's resident innate immune cells and also have a role in synaptic plasticity. Microglial processes continuously survey the brain parenchyma, interact with synaptic elements and maintain tissue homeostasis. However, the mechanisms that control surveillance and its role in synaptic plasticity are poorly understood. Microglial dynamics in vivo have been primarily studied in anesthetized animals. Here we report that microglial surveillance and injury response are reduced in awake mice as compared to anesthetized mice, suggesting that arousal state modulates microglial function. Pharmacologic stimulation of β -adrenergic receptors recapitulated these observations and disrupted experience-dependent plasticity, and these effects required the presence of β -adrenergic receptors in microglia. These results indicate that microglial roles in surveillance and synaptic plasticity in the mouse brain are modulated by noradrenergic tone fluctuations between arousal states and emphasize the need to understand the effect of disruptions of adrenergic signaling in neurodevelopment and neuropathology.
Editor: United States: Nature Publishing Group
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Noradrenergic signaling in the wakeful state inhibits microglial surveillance and synaptic plasticity in the mouse visual cortex

Stowell, Rianne D ; Sipe, Grayson O ; Dawes, Ryan P ; Batchelor, Hanna N ; Lordy, Katheryn A ; Whitelaw, Brendan S ; Stoessel, Mark B ; Bidlack, Jean M ; Brown, Edward ; Sur, Mriganka ; Majewska, Ania K

United States: Nature Publishing Group

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