Astrocytic Ca2+ signals partake in inhibitory neurovascular coupling in a brain state-dependent manner.

Abstract

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 this inhibitory NVC is unclear. We performed two-photon microscopy in awake mice to examine the correlation between astrocytic Ca2+ and NVC, evoked by activity in either all (VGATIN) or parvalbumin-positive GABAergic interneurons (PVIN). Optogenetic stimulation of VGATIN and PVIN in the somatosensory cortex triggered astrocytic Ca2+ increases that were abolished by anaesthesia. PVIN evoked astrocytic Ca2+ responses with a short latency that preceded NVC, whereas VGATIN evoked Ca2+ increases that were delayed relative to the NVC response. The early onset in PVIN evoked Ca2+ increases dependent on noradrenaline release from locus coeruleus, which also affected inhibitory NVC. Therefore, NVC mechanisms should be studied in awake mice and, though the relationship between interneuron activity and astrocytic Ca2+ is complex, we found a correlation between astrocyte activity and NVC in PVIN.