Jk. Elmquist et al., LEPTIN ACTIVATES DISTINCT PROJECTIONS FROM THE DORSOMEDIAL AND VENTROMEDIAL HYPOTHALAMIC NUCLEI, Proceedings of the National Academy of Sciences of the United Statesof America, 95(2), 1998, pp. 741-746
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.