Distinct populations of presympathetic-premotor neurons express orexin or melanin-concentrating hormone in the rat lateral hypothalamus

Abstract

Orexin and melanin-concentrating hormone (MCH) have been implicated in mediating a variety of different behaviors. These include sleep and wakefulness, locomotion, ingestive behaviors, and fight-or-flight response, as well as anxiety- and panic-like behaviors in rodents. Despite such diversity, all these processes require coordinated recruitment of the autonomic and somatomotor efferents. We have previously mapped the locations of presympathetic-premotor neurons (PSPMNs) in the rat brain. These putative dual-function neurons send trans-synaptic projections to somatomotor and sympathetic targets and likely participate in somatomotor-sympathetic integration. A significant portion of these neurons is found within the dorsomedial (DMH) and lateral hypothalamus (LH), areas of the brain that contain MCH- and orexin- synthesizing neurons in the central nervous system. Thus, we hypothesized that hypothalamic PSPMNs utilize MCH or orexin as their neurotransmitter. To test this hypothesis, we identified PSPMNs by using recombinant strains of the pseudorabies virus (PRV) for trans-synaptic tract tracing. PRV-152, a strain that expresses enhanced green fluorescent protein, was injected into sympathectomized gastrocnemius muscle, whereas PRV-BaBlu, which expresses beta-galactosidase, was injected into the adrenal gland in the same animals. By using immunofluorescent methods, we determined whether co-infected neurons express MCH or orexin. Our findings demonstrate that PSPMNs synthesizing either MCH or orexin are present within LH, where they form two separate populations. PSPMNs located around the fornix express orexin, whereas those located around the cerebral peduncle are more likely to express MCH. These two clusters of PSPMNs within LH likely play distinct functional roles in autonomic homeostasis and stress coping mechanisms.