Lateral hypothalamic Orexin-A-ergic projections to the arcuate nucleus modulate gastric function in vivo

It has been well-known that hypothalamic orexigenic neuropeptides, orexin-A, and melanin-concentrating hormone (MCH), play important roles in regulation of gastric function. However, what neural pathway mediated by the two neuropeptides affects the gastric function remains unknown. In this study, by way of nucleic stimulation and extracellular recording of single unit electrophysiological properties, we found that electrically stimulating the lateral hypothalamic area (LH) or microinjection of orexin-A into the arcuate nucleus (ARC) excited most gastric distension-responsive neurons in the nuclei and enhanced the gastric function including motility, emptying, and acid secretion of conscious rats. The results indicated that LH-ARC orexin-A-ergic projections may exist and the orexin-A in the ARC affected afferent and efferent signal transmission between ARC and stomach. As expected, combination of retrograde tracing and immunohistochemistry showed that some orexin-A-ergic neurons projected from the LH to the ARC. In addition, microinjection of MCH and its receptor antagonist PMC-3881-PI into the ARC affected the role of orexin-A in the ARC, indicating a possible involvement of the MCH pathway in the orexin-A role. Our findings suggest that there was an orexin-A-ergic pathway between LH and ARC which participated in transmitting information between the central nuclei and the gastrointestinal tract and in regulating the gastric function of rats.