Role of neuropeptides in the regulation of hypothalamic neurovascular coupling: Physio-pathological implications
Javier Stern, M.D. Ph.D.
Director, Center for Neuroinflammation and Cardiometabolic Diseases (CNCD)
Georgia State University

Résumé : 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. Still, whether the conventional, rapid, and spatially restricted NVC response can be generalized to deeper and functionally diverse brain regions remains unknown. The hypothalamic supraoptic nucleus (SON) is a deep brain region with unique cytoarchitectural properties, including high vascularization. Paradoxically, the dense vascular network is not required to maintain its metabolic demand. This mismatch in metabolic supply and demand suggests that the SON vasculature may serve additional functions beyond the delivery of energy substrates. To address this important gap in our knowledge, we set up the objective to implement a novel experimental approach to enable in vivo, real-time two-photon imaging from the ventral surface of the brain to monitor SON NVC responses to a systemic homeostatic challenge. Using this approach in anaesthetized male and female transgenic rats expressing GFP driven by the vasopressin (AVP) promoter (AVP-GFP rats), we found that a systemic hypertonic saline (HTS) infusion evoked a gradual and linear increase in the firing rate of AVP neurons. Contrary to classical vasodilatory NVC, the increased AVP neuronal activity was accompanied by a significant intraparenchymal arteriole (but not venule) vasoconstriction. This “inverse” NVC was prevented when an AVP V1a receptor antagonist was locally delivered within the SON. The salt-induced inverse NVC response resulted in a rapid and progressive decrease in SON pO2 and increased expression of the hypoxia-inducible factor (HIF)-1α mRNA. Next, we examined the effect of salt in a chronic heart failure (HF) model, which is well known for its overactive vasopressin system. We hypothesized that salt would amplify the already activated vasopressin system. However, we found intraparenchymal arteriolar vasodilatation and a progressive increase in SON pO2. Moreover, the local (SON) application of adenosine A2A receptor antagonist abolished salt-induced vasodilatation in HF. Taken together, our results support a change in the polarity of the salt-induced NVC in HF rats, from vasoconstriction (AVP-mediated) to vasodilation (adenosine-mediated). The potential consequences of the salt-evoked iNVC in “upstream” cognitive-related brain regions, as well as the impact of the change in polarity during HF, will be discussed in my presentation.

Invité par Françoise Muscatelli & NeuroMarseille
Lundi 17 mars 2025 à 11h, salle de conférence de l’Inmed