Localised Astrocyte Ca2+ Activity Regulates Neurovascular Coupling Responses to Active Sensing.

Abstract

Neurovascular coupling (NVC) ensures sufficient and targeted blood flow during increased neuronal activity. Astrocytic participation in NVC has long been debated, likely due to the intricacy of the intracellular Ca2+ fluxes and the diversity of their regulatory capacities. As astrocyte signaling changes with brain states, we focused on their involvement in voluntary sensing in freely behaving mice. We used 2-photon microscopy to record cellular and vascular activity in the whisker barrel cortex of awake head-fixed animals. The NVC initiated by volitional whisking in the resting mouse was compared to the whisking preceding locomotion and experimenter-evoked whisker deflections. We developed an analysis method to detect early, subcellular astrocytic activity and found it corresponded with neuronal and vascular responses under all three conditions. After the depletion of noradrenaline (NA), the early astrocytic Ca2+ response to volitional whisking was only moderately reduced and primarily in astrocytic processes closest to the blood vessels. Meanwhile, the dilation of 1st order capillaries was also reduced. Together, these findings demonstrate significant disruptions in the focal regulation of cerebral blood flow, potentially limiting the sustenance of activated neurons. This disruption appeared to translate into behavioral aberrations, as NA-depleted mice exhibited an extended period of exploratory whisking prior to locomotion. Remarkably, NA-depletion did not alter cellular or blood flow responses to locomotion or experimenter-evoked whisking. Our study confirms an astrocytic contribution to NVC, which is relevant during volitional sensing. It also suggests that self-directed sensory processing depends on an appropriate NVC response, which itself depends on NA and astrocyte activity.