PV interneurons evoke astrocytic Ca2+ responses in awake mice, which contributes to neurovascular coupling

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 NVC caused by interneurons is unclear. While astrocyte Ca²⁺ 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 Ca²⁺ and NVC, evoked by activation of either all (VGAT_IN ) or only parvalbumin-positive GABAergic interneurons (PV_IN ). Optogenetic stimulation of VGAT_IN and PV_IN in the somatosensory cortex triggered astrocytic Ca²⁺ increases that were abolished by anesthesia. In awake mice, PV_IN evoked astrocytic Ca²⁺ responses with a short latency that preceded NVC, whereas VGAT_IN evoked Ca²⁺ increases that were delayed relative to the NVC response. The early onset of PV_IN evoked astrocytic Ca²⁺ increases depended on noradrenaline release from locus coeruleus as did the subsequent NVC response. Though the relationship between interneuron activity and astrocytic Ca²⁺ responses is complex, we suggest that the rapid astrocyte Ca²⁺ responses to increased PV_IN activity shaped the NVC. Our results underline that interneuron and astrocyte-dependent mechanisms should be studied in awake mice.

Keywords: astrocytes; brain states; inhibitory interneurons; neurovascular coupling; noradrenaline.