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Noradrenergic signaling acts through astrocytes to modulate cortical activity and state

Abstract

There is growing evidence that non-neuronal cells in the nervous system, particularly astrocytes, have their own distinct patterns of activity and may act as additional players in the physiological functioning of neural circuits. However, the drivers and pattern of physiological astrocyte activity, its relationship to neuromodulatory signaling and local circuit activity, and its role in neural circuits is not known. Using a combination of in vivo two-photon imaging, electrophysiology, pharmacology, and genetic and chemogenetic perturbations in mouse visual cortex, I describe structured astrocyte activity patterns driven by the monoamine norepinephrine across behavioral states which alters the level and pattern of activity in the nearby cortical circuit. These results likely extend bi-hemispherically through an inhibitory pathway downstream of astrocyte activity. In sum, this work indicates astrocytes act as a distinct neuromodulatory pathway for regulating the amount and pattern of nearby neuronal activity in the typical wakeful functioning of the cortex, and builds on a growing literature directly implicating astrocytes as crucial components in neural circuits.

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