Chemically defined projections linking the mediobasal hypothalamus and thelateral hypothalamic area

Recent studies have identified several neuropeptide systems in the hypothal amus that are critical in the regulation of body weight. The lateral hypoth alamic area (LHA) has long been considered essential in regulating food int ake and body weight. Two neuropeptides, melanin-concentrating hormone (MCH) and the orexins (ORX), are localized in the LHA and provide diffuse innerv ation of the neuraxis, including monosynaptic projections to the cerebral c ortex and autonomic preganglionic neurons; Therefore, MCH and ORX neurons m ay regulate both cognitive and autonomic aspects of food intake and body we ight regulation. The arcuate nucleus also is critical in the regulation of body weight, because it contains neurons that express leptin receptors, neu ropeptide Y (NPY), alpha-melanin-stimulating hormone (alpha-MSH), and agout i-related peptide (AgRP). In this study, we examined the relationships of t hese peptidergic systems by using dual-label immunohistochemistry or in sit u hybridization in rat, mouse, and human brains. In the normal rat, mouse, and human brain, ORX and MCH neurons make up segregated populations. In add ition, we found that AgRP- and NPY-immunoreactive neurons are present in th e medial division of the human arcuate nucleus, whereas alpha-MSH-immunorea ctive neurons are found in the lateral arcuate nucleus. In humans, AgRP pro jections were widespread in the hypothalamus, but they were especially dens e in the paraventricular nucleus and the perifornical area. Moreover, in bo th rat and human, MCH and ORX neurons receive innervation from NPY-, AgRP-, and alpha-MSH-immunoreactive fibers. Projections from populations of lepti n-responsive neurons in the mediobasal hypothalamus to MCH and ORX cells in the LHA may link peripheral metabolic cues with the cortical mantle and ma y play a critical role in the regulation of feeding behavior and body weigh t. J. Comp. Neurol. 402:442-459, 1998. (C) 1998 Wiley-Liss, Inc.