Type-I nNOS neurons orchestrate cortical neural activity and vasomotion

It is unknown how the brain orchestrates the coordination of global neural and vascular dynamics. We sought to uncover the role of a sparse but unusual population of genetically-distinct interneurons known as type-I nNOS neurons, using a novel pharmacological strategy to unilaterally ablate these neurons from the somatosensory cortex of mice. Region-specific ablation produced changes in both neural activity and vascular dynamics, decreased power in the delta-band of the local field potential, reduced sustained vascular responses to prolonged sensory stimulation, and abolished the post-stimulus undershoot in cerebral blood volume. Coherence between the left and right somatosensory cortex gamma-band power envelope and blood volume at ultra-low frequencies was decreased, suggesting that type-1 nNOS neurons integrate long-range coordination of brain signals. Lastly, we observed decreases in the amplitude of resting-state blood volume oscillations and decreased vasomotion following the ablation of type-I nNOS neurons. This demonstrates that a small population of nNOS-positive neurons is indispensable for regulating both neural and vascular dynamics in the whole brain and implicates disruption of these neurons in diseases ranging from neurodegeneration to sleep disturbances.