A large number of studies have implicated the lower brainstem, and particularly the vagal complex of the medulla oblongata, in the central control of blood glucose levels and in the glucoprivic regulation of feeding. Within the vagal complex the nucleus of the solitary tract which is a major relay station for ascending visceral and cardiovascular homeostatic signals, and the dorsal vagal motor nucleus, which is the source of the vagal efferent fibers projecting to most visceral organs, including liver and pancreas, are of particular interest. Like several hypothalamic nuclei, these structures within the dorsal vagal complex contain glucose-inhibited and glucose-excited neurons. However, relatively little is known about the molecular components involved in glucose sensing and in generating the electrical signal. Utilizing primarily rodent in vitro brainslice preparations we investigate whether specific brainstem cell populations are intrinsically sensitive to physiological changes in glucose availability. We explore which molecular and electrical pathways are responsible for this sensitivity and how it relates to their general metabolic sensitivity. This involves the combination of patch-clamp electrophysiology with single-cell RT-PCR and immunocytochemistry. Our results indicate that brainstem responses to hypoglycemia are elicited at higher glucose levels than in hypothalamic nuclei. They also demonstrate the involvement of glucokinase and the activation of ATP-sensitive K⁺channels in the hypoglycemia response of glucose-excited neurons and suggest a variety of different mechanisms, including, but not limited to, inhibition of 2-pore-domain K⁺channels, in glucose-inhibited cells. We are using transgenic mouse models to ascertain the involvement of specific ion channels and to characterize the responses of specific cell populations.