PV interneurons evoke astrocytic Ca 2+ responses in awake mice, which contributes to neurovascular coupling.

Neurovascular coupling (NVC) modulates cerebral blood flow to match increased metabolic demand during neuronal excitation. Activation of inhibitory interneurons also increase blood flow, but the basis for NVC caused by interneurons is unclear. While astrocyte Ca levels rise with excitatory neural transmission, much less is known with regards to astrocytic sensitivity to inhibitory neurotransmission. We performed two-photon microscopy in awake mice to examine the correlation between astrocytic Ca and NVC, evoked by activation of either all (VGAT ) or only parvalbumin-positive GABAergic interneurons (PV ). Optogenetic stimulation of VGAT and PV in the somatosensory cortex triggered astrocytic Ca increases that were abolished by anesthesia. In awake mice, PV evoked astrocytic Ca responses with a short latency that preceded NVC, whereas VGAT evoked Ca increases that were delayed relative to the NVC response. The early onset of PV evoked astrocytic Ca increases depended on noradrenaline release from locus coeruleus as did the subsequent NVC response. Though the relationship between interneuron activity and astrocytic Ca responses is complex, we suggest that the rapid astrocyte Ca responses to increased PV activity shaped the NVC. Our results underline that interneuron and astrocyte-dependent mechanisms should be studied in awake mice.