Norepinephrine links astrocytic activity to regulation of cortical state
Description
Cortical state, defined by population-level neuronal activity patterns, determines sensory perception. While arousal-associated neuromodulators—including norepinephrine (NE)—reduce cortical synchrony, how the cortex resynchronizes remains unknown. Furthermore, general mechanisms regulating cortical synchrony in the wake state are poorly understood. Using in vivo imaging and electrophysiology in mouse visual cortex, we describe a critical role for cortical astrocytes in circuit resynchronization. We characterize astrocytes' calcium responses to changes in behavioral arousal and NE, and show that astrocytes signal when arousal-driven neuronal activity is reduced and bi-hemispheric cortical synchrony is increased. Using in vivo pharmacology, we uncover a paradoxical, synchronizing response to Adra1a receptor stimulation. We reconcile these results by demonstrating that astrocyte-specific deletion of Adra1a enhances arousal-driven neuronal activity, while impairing arousal-related cortical synchrony. Our findings demonstrate that astrocytic NE signaling acts as a distinct neuromodulatory pathway, regulating cortical state and linking arousal-associated desynchrony to cortical circuit resynchronization.
Notes
All data are two-photon imaging, electrophysiology, and associated physiology datasets. All data is formatted to allow for reconstructing the figures in Reitman et al. 2022 with limited user input needed. Data are stored as MAT-Files and the linked code was generated in MATLAB 2020a. The data for each figure is separated into individual MAT-Files, and should be placed in the same folder as the linked code. Running the 'MakeFigures.m' file will result in all Paper figures being created, and to create individual figures one can run the 'PlotFigX.m' function within 'MakeFigures.m'. Abbreviations used in file names: xcorr = cross-correlation; ETA = event-triggered average; floxed = Adra1afl/fl
Funding provided by: National Institute of Neurological Disorders and Stroke
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000065
Award Number: R01NS099254
Funding provided by: National Institute of Mental Health
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000025
Award Number: R01MH121446
Funding provided by: National Science Foundation
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000001
Award Number: CAREER 1942360
Funding provided by: UCSF Program for Breakthrough Biomedical Research*
Crossref Funder Registry ID:
Award Number: n/a
Funding provided by: Genentech Fellowship*
Crossref Funder Registry ID:
Award Number: n/a
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Additional details
Related works
- Is cited by
- 10.1038/s41593-023-01284-w (DOI)