Inverse neurovascular coupling contributes to positive feedback excitation of vasopressin neurons during a systemic homeostatic challenge.

Neurovascular coupling (NVC), the process that links neuronal activity to cerebral blood flow changes, has been mainly studied in superficial brain areas, namely the neocortex. Whether the conventional, rapid, and spatially restricted NVC response can be generalized to deeper and functionally diverse brain regions remains unknown. Implementing an approach for in vivo two-photon imaging from the ventral surface of the brain, we show that a systemic homeostatic challenge, acute salt loading, progressively increases hypothalamic vasopressin (VP) neuronal firing and evokes a vasoconstriction that reduces local blood flow. Vasoconstrictions are blocked by topical application of a VP receptor antagonist or tetrodotoxin, supporting mediation by activity-dependent, dendritically released VP. Salt-induced inverse NVC results in a local hypoxic microenvironment, which evokes positive feedback excitation of VP neurons. Our results reveal a physiological mechanism by which inverse NVC responses regulate systemic homeostasis, further supporting the notion of brain heterogeneity in NVC responses.