Multicore fiber optic imaging reveals that astrocyte calcium activity in the cerebral cortex is modulated by internal motivational state

Astrocytes are a direct target of neuromodulators and can influence neuronal activity on broad spatial and temporal scales through their close proximity to synapses. However, our knowledge about how astrocytes are functionally recruited during different animal behaviors and their diverse effects on the CNS remains limited. To enable measurement of astrocyte activity patterns in vivo during normative behaviors, we developed a high-resolution, long working distance, multi-core fiber optic imaging platform that allows visualization of cortical astrocyte calcium transients through a cranial window in freely moving mice. Using this platform, we defined the spatiotemporal dynamics of astrocytes during diverse behaviors, ranging from circadian fluctuations to novelty exploration, showing that astrocyte activity patterns are more variable and less synchronous than apparent in head-immobilized imaging conditions. Although the activity of astrocytes in visual cortex was highly synchronized during quiescence to arousal transitions, individual astrocytes often exhibited distinct thresholds and activity patterns during explorative behaviors, in accordance with their molecular diversity, allowing temporal sequencing across the astrocyte network. Imaging astrocyte activity during self-initiated behaviors revealed that noradrenergic and cholinergic systems act synergistically to recruit astrocytes during state transitions associated with arousal and attention, which was profoundly modulated by internal state. The distinct activity patterns exhibited by astrocytes in the cerebral cortex may provide a means to vary their neuromodulatory influence in response to different behaviors and internal states.