Parvalbumin interneurons drive depth-dependent vascular responses

Understanding how neurons regulate cerebral blood flow (CBF) is crucial for interpreting brain hemodynamic imaging signals. Although parvalbumin (PV) interneurons strongly influence network activity, their effects on CBF appear variable, particularly during natural sensory stimulation and resting state. Using two-photon imaging in awake mice, we assessed PV interneuron effects on vascular tone across cortical depths during evoked and spontaneous activity. Optogenetic PV activation produced rapid vasodilation in the superficial cortex (<250 μm) and slow, delayed vasodilation in the middle cortex (250-400 μm). Chemogenetic PV suppression revealed that PV interneurons did not drive the rapid hemodynamic increase to sustained sensory input but did contribute to superficial vasodilation following brief stimuli. During spontaneous activity, synchronized PV interneuron activity predicted depth-specific arteriolar changes more strongly than non-PV neurons. These findings demonstrate a depth-dependent role for PV interneurons in regulating CBF and refine our understanding of neurovascular coupling.