Norepinephrine Links Astrocytic Activity to Regulation of Cortical State

Overview

Journal Nat Neurosci

Date 2023 Mar 30

PMID 36997759

Authors

Michael E Reitman

Vincent Tse

Xuelong Mi

Drew D Willoughby

Alba Peinado

Alexander Aivazidis

Bat-Erdene Myagmar

Paul C Simpson

Omer A Bayraktar

Guoqiang Yu

Kira E Poskanzer

Affiliations

Soon will be listed here.

Abstract

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.

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