Bidirectional control of neurovascular coupling by cortical somatostatin interneurons

Neurovascular coupling, linking neuronal activity to cerebral blood flow, is altered early in neurological disorders and underlies functional brain imaging. This process involves numerous cellular players. Among them inhibitory interneurons receive increasing attention, but how they control blood flow remains elusive. This study elucidates the mechanisms by which somatostatin interneurons bidirectionally control neurovascular coupling. Patch clamp recordings in, ex vivo, cortical slices from mice expressing channelrhodopsin-2 in somatostatin interneurons, revealed that these neurons are supralinearly activated at low-frequencies (< 5 Hz) and efficiently photostimulated at frequencies up to 20 Hz. Ex vivo vascular imaging showed that low-frequency (2 Hz) photostimulation triggered vasodilation whereas high-frequency (20 Hz) photostimulation induced vasoconstriction. Histochemistry revealed that subpopulations of cortical somatostatin interneurons expressed the neuronal nitric oxide synthase, and/or neuropeptide Y to a greater extent. Consistently, pharmacological investigations showed that vasodilation induced by low-frequency photostimulation involves nitric oxide release and activation of soluble guanylate cyclase. In contrast, the vasoconstriction induced at high-frequency photostimulation involves neuropeptide Y release and activation of the Y1 vascular receptor. These findings provide valuable insights into neurovascular coupling and help to understand the cellular mechanism underlying the functional brain imaging signals.