LEPTIN ACTIVATES DISTINCT PROJECTIONS FROM THE DORSOMEDIAL AND VENTROMEDIAL HYPOTHALAMIC NUCLEI

Leptin has profound effects on feeding, metabolism, and neuroendocrine status, Evidence indicates that the hypothalamus coordinates these re sponses, though the specific brain pathways engaged by leptin remain o bscure, The paraventricular nucleus of the hypothalamus (PVH) regulate s pituitary gland function and feeding, and innervates autonomic prega nglionic neurons, making it a candidate to regulate many of the respon ses to leptin, The subparaventricular zone, an anterior hypothalamic r egion receiving dense innervation from the suprachiasmatic nucleus, is thought to integrate circadian and metabolic information, We investig ated the distribution of neurons in the rat brain activated by leptin administration that also project to the PVH or the subparaventricular zone by coupling immunohistochemistry for Fos with retrograde transpor t of cholera toxin-b, Intravenous leptin characteristically activated several cell groups including the ventromedial hypothalamic nucleus, t he dorsomedial hypothalamic nucleus (DMH), and the PVH, When tracer in jections were centered in the subparaventricular zone, many double-lab eled cells were observed in the dorsomedial subdivision of the ventrom edial hypothalamic nucleus. This projection may provide an anatomic su bstrate for integration of metabolic and circadian information to regu late the hypothalamo-pituitary axis, When cholera toxin-b injections w ere centered in the PVH, many double-labeled cells were found within t he caudal DMH. Hence, activation of specific neuroendocrine and autono mic elements of the PVH may be triggered by leptin-activated afferents arising in the DMH. Our results demonstrate that a discrete set of hy pothalamic pathways may underlie leptin's autonomic, endocrine, and be havioral effects.