The subfornical organ (SFO) is a sensory circumventricular organ located along the anterodorsal wall of the third ventricle. SFO lacks a complete blood-brain barrier (BBB), and thus peripherally-circulating factors can penetrate the SFO parenchyma. These signals are detected by local neurons providing the brain with information from the periphery to mediate central responses to humoral signals and physiological stressors. Circumventricular organs are characterized by the presence of unique populations of non-neuronal cells, such as tanycytes and fenestrated endothelium. However, how these populations are organized within the SFO is not well understood. In this study, we used histological techniques to analyze the anatomical organization of the rat SFO and examined the distribution of neurons, fenestrated and non-fenestrated vasculature, tanycytes, ependymocytes, glia cells, and pericytes within its confines. Our data show that the shell of SFO contains non-fenestrated vasculature, while fenestrated capillaries are restricted to the medial-posterior core region of the SFO and associated with a higher BBB permeability. In contrast to non-fenestrated vessels, fenestrated capillaries are encased in a scaffold created by pericytes and embedded in a network of tanycytic processes. Analysis of c-Fos expression following systemic injections of angiotensin II or hypertonic NaCl reveals distinct neuronal populations responding to these stimuli. Hypertonic NaCl activates ∼13% of SFO neurons located in the shell. Angiotensin II-sensitive neurons represent ∼35% of SFO neurons and their location varies between sexes. Our study provides a comprehensive description of the organization of diverse cellular elements within the SFO, facilitating future investigations in this important brain area.

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