Astrocyte Contribution to Brain State-Dependent Neurovascular Coupling

The process of neurovascular coupling (NVC) is the regulation of sufficient and targeted blood flow during energy-consuming cerebral processes. Astrocyte participation in NVC has long been debated. The lack of clear answers is likely based on the diversity of astrocyte intracellular Ca2+ activities and the multitude of ways astrocytes may regulate cerebral blood flow. We focused our investigation on NVC responses to sensory input actively reached for by freely behaving mice. To do so, we studied the cellular and vascular activity in the sensory whisker barrel cortex of awake head-fixed mice and aligned this activity to the volitional whisking events. We compared the NVC initiated by the whisking event in the resting mouse to the whisking evoked by the experimenter and the whisking prior to locomotion. We did this comparison because astrocyte signaling is known to be sensitive to brain state transitions. In the NVC response to all three, we found that both neuronal and astrocytic activity corresponded to vascular activity. When we repeated this investigation after depletion of NA release from locus coeruleus projections, we identified that the three NVC responses did not equally depend on NA delivery or astrocytic activity. Though we found the expected effect on astrocytic Ca2+ surges, the whisking- dependent astrocytic Ca2+ activity was only moderately reduced by the reduced NA levels in the resting mouse and only in cells near the vessels. On the vascular side, we found that the dilation of the 1st order capillary to volitional whisking was much reduced. This suggests a disturbance in the precision regulation of the cerebral blood flow that may limit the appropriate delivery of blood to the region of activated neurons. Finally, this disturbance might partially account for the extended period of exploratory whisking prior to the initiation of locomotion that we saw in the NA-depleted mice. Our study reveals an astrocytic contribution to NVC in the natural shifts in the attention directed toward the sensory input received during volitional whisking. ### Competing Interest Statement The authors have declared no competing interest.