PV interneurons evoke astrocytic Ca2+ 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 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 (VGATIN ) or only parvalbumin-positive GABAergic interneurons (PVIN ). Optogenetic stimulation of VGATIN and PVIN in the somatosensory cortex triggered astrocytic Ca2+ increases that were abolished by anesthesia. In awake mice, 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 of PVIN 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 PVIN activity shaped the NVC. Our results underline that interneuron and astrocyte-dependent mechanisms should be studied in awake mice.

Modification of oxygen consumption and blood flow in mouse somatosensory cortex by cell-type-specific neuronal activity.

Gamma activity arising from the interplay between pyramidal neurons and fast-spiking parvalbumin (PV) interneurons is an integral part of higher cognitive functions and is assumed to contribute significantly to brain metabolic responses. Cerebral metabolic rate of oxygen (CMRO2) responses were evoked by optogenetic stimulation of cortical PV interneurons and pyramidal neurons. We found that CMRO2 responses depended on neuronal activation, but not on the power of gamma activity induced by optogenetic stimulation. This implies that evoked gamma activity per se is not energy demanding. Optogenetic stimulation of PV interneurons during somatosensory stimulation reduced excitatory neuronal activity but did not potentiate O2 consumption as previously hypothesized. In conclusion, our data suggest that activity-driven CMRO2 responses depend on neuronal excitation rather than the cerebral rhythmic activity they induce. Excitation of both excitatory and inhibitory neurons requires energy, but inhibition of cortical excitatory neurons by interneurons does not potentiate activity-driven energy consumption.