Circumventricular organs: Targets for integration of circulating fluid and energy balance signals?

• SFO interfaces with circulating signals that do not cross the blood brain barrier.
• Circulating indicators of cardiovascular/metabolic status influence SFO neurons.
• Sensitivity to these circulating signals is modified by physiological state.
• We suggest integrative roles for SFO neurons in controlling ingestive behavior.

The subfornical organ (SFO), as one of the sensory circumventricular organs (CVOs), is among the only central nervous system structures which interfaces directly with circulating substances that do not cross the blood brain barrier. Here we describe a growing literature showing that circulating indicators of cardiovascular (angiotensin II, osmolarity, calcium, sodium) and metabolic (adiponectin, amylin, glucose, ghrelin, leptin) statuses influence the excitability of single SFO neurons. Single cell electrophysiological studies from our laboratory have demonstrated excitatory effects of angiotensin II on individual SFO neurons, and changes in angiotensin II receptor expression in this CVO in hypertensive states emphasize the dynamic contribution of SFO neurons to the regulation of fluid balance. Furthermore, we have shown both depolarizing and hyperpolarizing effects of the adipokines adiponectin and leptin in SFO cells, and highlight that conditions of fasting in the case of adiponectin, and obesity in the case of leptin, alter the sensitivity of SFO neurons to these circulating factors. The results examined in this review provide evidence for a role of the SFO as a mediator and integrative structure in the maintenance of cardiovascular and metabolic functions.