Fig. 4

Neurocircuitry of VMH neurons in glucose homeostasis and other homeostatic responses. Optogenetic stimulation of VMH neurons induces hyperglycemia via projections from SF1 neurons to the anterior bed nucleus of the stria terminalis (aBNST), as well as projections from NOS1 neurons to aBNST and the periaqueductal gray (PAG). Glucose-sensing neurons are enriched in the ARH-ME and brainstem, i.e., area postrema (AP) and nucleus of solitary tract (NTS), such that these neurons can detect changes in the circulating glucose level directly. Glucose-sensing neurons in the ARH-ME send projections to the VMH. Meanwhile, neurons in the VMH also receive efferent inputs from the lateral parabrachial nucleus (LPBN), where it may receive projections from AP and NTS regarding changes of circulating glucose level. There is a possibility that NTS neurons might also receive inputs from glucose sensors in the gastrointestinal gut via afferent vagal nerve. It is still under debate whether glucose-sensing neurons in the VMH can sense the blood glucose fluctuations directly before efferent responses are mounted. For other homeostatic responses, activation of SF1 neurons is also involved in suppression of food intake via projection to the paraventricular thalamus (PVT). SF1 neurons projection to the PAG induces inflexible immobility, and to anterior hypothalamic nucleus (AHN) pathway promotes avoidance. Red dots represent glucose-sensing neurons. The figure is created in BioRender.com