Insulin modulates the electrical activity of subfornical organ neurons

Insulin plays a crucial role in the regulation of energy balance. Within the central nervous system, hypothalamic nuclei such as the arcuate and ventromedial nuclei are targets of insulin; however, insulin may only access these nuclei after transport across the blood-brain barrier. Neurons of the subfornical organ are not protected by the blood-brain barrier and can rapidly detect and respond to circulating hormones such as leptin and ghrelin. Moreover, subfornical organ neurons form synaptic connections with hypothalamic control centers that regulate energy balance, including the arcuate and dorsomedial nuclei. However, it is unknown whether subfornical organ neurons respond to insulin. Using whole-cell current clamp, we examined the electrophysiological effects of insulin on rat subfornical organ neurons. Upon insulin application, 70% of neurons tested were responsive, with 33% of neurons tested (9/27) exhibiting hyperpolarization of membrane potential (-8.7 ± 1.7 mV) and 37% (10/27) exhibiting depolarization (10.5 ± 2.8 mV). Using pharmacological blockade, our data further indicate that the hyperpolarization was mediated by opening of KATP channels, whereas depolarization resulted from opening of Ih channels. These data are the first to show that insulin exerts a direct effect on the electrical activity of subfornical organ neurons and support the notion that the subfornical organ may act to communicate information on circulating satiety signals to homeostatic control centers.