Astrocyte cell volume dynamics across cortical states and transitions

The sleep-wake cycle subdivides brain activity into distinct states of neural circuit activity, fluid transport, and interstitial-volume fraction. We used in vivo two-photon imaging of mice to ask whether cortical astrocytes exhibit state-dependent volume changes. Our analysis showed that the astrocyte volume expands during wakefulness and shrinks during non-rapid eye movement (NREM) sleep and even more during rapid eye movement (REM) sleep. Norepinephrine (NE) exhibited state-dependent fluctuations that were mirrored by the corresponding changes in astrocytic volume. Pharmacologically blockage of α1-adrenergic, but not α2- or β-adrenergic, receptors, resulted in astrocyte shrinkage. Both chemogenetic and optogenetic stimulation of tyrosine hydroxylase (TH)-positive neurons in the locus coeruleus (LC) significantly increased cortical astrocytic cell volume, which was abolished by the α1-receptor antagonist prazosin. We propose that astrocytic expansion during wakefulness, driven by NE leads to a corresponding shrinkage of the interstitial-volume fraction, increasing neuroglia interactions and suppressing glymphatic flow.