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Type-I nNOS neurons orchestrate cortical neural activity and vasomotion

Kevin L. Turner,Dakota Brockway,Md Shakhawat Hossain,Keith R. Griffith,D. Greenawalt,Qingguang Zhang,Kyle W. Gheres,Nicole Crowley,Patrick J. Drew

Published 2025 in eLife

ABSTRACT

It is unknown how the brain orchestrates 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 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, raising the possibility that loss of these neurons could contribute to the development of neurodegenerative diseases and sleep disturbances.

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