title: Orexin inputs to caudal raphé neurons involved in thermal, cardiovascular, and gastrointestinal regulation.
abstract: Orexin-expressing neurons in the lateral hypothalamus with their wide projections throughout the brain are important for the regulation of sleep and wakefulness, ingestive behavior, and the coordination of these behaviors in the environmental context. To further identify downstream effector targets of the orexin system, we examined in detail orexin-A innervation of the caudal raphe nuclei in the medulla, known to harbor sympathetic preganglionic motor neurons involved in thermal, cardiovascular, and gastrointestinal regulation. All three components of the caudal raphe nuclei, raphe pallidus, raphe obscurus, and parapyramidal nucleus, are innervated by orexin-A-immunoreactive fibers. Using confocal microscopy, we demonstrate close anatomical appositions between varicose orexin-A immunoreactive axon profiles and sympathetic premotor neurons identified with either a transneuronal retrograde pseudorabies virus tracer injected into the interscapular brown fat pads, or with in situ hybridization of pro-TRH mRNA. Furthermore, orexin-A injected into the fourth ventricle induced c-Fos expression in the raphe pallidus and parapyramidal nucleus. These findings suggest that orexin neurons in the hypothalamus can modulate brown fat thermogenesis, cardiovascular, and gastrointestinal functions by acting directly on neurons in the caudal raphe nuclei, and support the idea that orexin's simultaneous stimulation of food intake and sympathetic activity might have evolved as a mechanism to stay alert while foraging.
authors.affiliation: Neurobiology of Nutrition Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA. berthohr@pbrc.edu
authors.forename: Hans-Rudolf
authors.initials: HR
authors.lastname: Berthoud
authors.forename: Laurel M
authors.initials: LM
authors.lastname: Patterson
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Sutton
authors.forename: Christopher
authors.initials: C
authors.lastname: Morrison
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Zheng
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D002320:Cardiovascular Physiological Phenomena; D041981:Gastrointestinal Tract / Q000502:physiology*; D015870:Gene Expression; D007150:Immunohistochemistry; D017403:In Situ Hybridization / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis / Q000494:pharmacology / Q000502:physiology*; D018613:Microscopy, Confocal; D009474:Neurons / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D009479:Neuropeptides / Q000032:analysis / Q000494:pharmacology / Q000502:physiology*; D000068797:Orexins; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000166:cytology / Q000502:physiology; D022722:Thermogenesis; D013973:Thyrotropin-Releasing Hormone / Q000235:genetics
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D013973:Thyrotropin-Releasing Hormone
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