Norepinephrine links astrocytic activity to regulation of cortical state

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.