Inverse Neurovascular Coupling Contributes to Positive Feedback Excitation of Vasopressin Neurons in Response to a Systemic Homeostatic Challenge

Abstract

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 a novel approach that enables in vivo two-photon imaging from the ventral surface of the brain, we show that a systemic homeostatic challenge, acute salt loading, progressively increased hypothalamic vasopressin neuronal firing and evoked a vasoconstriction that reduced local blood flow. Vasoconstrictions were blocked by topical application of a vasopressin receptor antagonist or tetrodotoxin, supporting mediation by activity-dependent, dendritically-released vasopressin. Salt-induced inverse NVC resulted in a local hypoxic microenvironment, which evoked positive feedback excitation of vasopressin neurons. Our results reveal a novel physiological mechanism by which inverse NVC responses regulate systemic homeostasis, further supporting the notion of brain heterogeneity in NVC responses.