Long-range inhibitory neurons mediate cortical neurovascular coupling

To meet the high energy demands of brain function, cerebral blood flow (CBF) parallels changes in neuronal activity by a mechanism known as neurovascular coupling (NVC). However, which neurons play a role in mediating NVC is not well understood. Here, we identify in mice and humans a specific population of cortical GABAergic neurons that co-express neuronal nitric oxide synthase and tachykinin receptor 1 (Tacr1). Through whole-tissue clearing, we demonstrate that Tacr1 neurons extend local and long-range projections across functionally connected cortical areas. We show that whisker stimulation elicited Tacr1 neuron activity in the barrel cortex through feedforward excitatory pathways. Additionally, through optogenetic experiments, we demonstrate that Tacr1 neurons are instrumental in mediating CBF through the relaxation of mural cells in a similar fashion to whisker stimulation. Finally, by electron microscopy, we observe that Tacr1 processes contact astrocytic endfeet. These findings suggest that Tacr1 neurons integrate cortical activity to mediate NVC. [Display omitted] •Tacr1 neurons are long-range-projecting somatostatin neurons that co-express Nos1 and NPY•Tacr1 neurons receive input from excitatory neurons and respond to sensory stimulation•Tacr1 neurons are strong regulators of cerebral blood flow•Tacr1 neurons regulate vasodilation via pericyte and vascular smooth muscle relaxation Ruff et al. identify a subpopulation of inhibitory neurons, Tacr1 neurons, that regulate cerebral blood flow. Tacr1 neurons are long-range-projecting neurons that use feedforward excitatory pathways to mediate neurovascular coupling.