title: Expression of the M3 Muscarinic Receptor on Orexin Neurons that Project to the Rostral Ventrolateral Medulla.
abstract: Activation of central cholinergic receptors causes a pressor response in rats, and the hypothalamus is important for this response. Projections from hypothalamic orexin neurons to the rostral ventrolateral medulla (RVLM) are involved in sympatho-excitation of the cardiovascular system. A small population of orexin neurons is regulated by cholinergic inputs through M3 muscarinic acetylcholine receptor (M3 R). To elucidate whether the M3 R on orexin neurons is involved in cardiosympathetic regulation through the RVLM, we examined the presence of the M3 R on retrograde-labeled RVLM-projecting orexin neurons. The retrograde tracer was unilaterally injected into the RVLM. Within the hypothalamus, retrograde-labeled neurons were located predominantly ipsilateral to the injection side. In the anterior hypothalamus (-1.5 to -2.3 mm to the bregma), retrograde-labeled neurons were densely distributed in the paraventricular nuclei and scattered in the retrochiasmatic area. At -2.3 to -3.5 mm from the bregma, labeled neurons were located in the regions where orexin neurons were situated, that is, the tuberal lateral hypothalamic area, perifornical area, and dorsomedial nuclei. Very few retrograde-labeled neurons were observed in the hypothalamus at -3.5 to -4.5 mm from the bregma. About 19.5% ± 1.6% of RVLM-projecting neurons in the tuberal hypothalamus were orexinergic. The M3 R was present on 18.7% ± 3.0% of RVLM-projecting orexin neurons. Injection of a muscarinic agonist, oxotremorine, in the perifornical area resulted in a pressor response, which was attenuated by a pretreatment of atropine. We conclude that cholinergic inputs to orexin neurons may be involved in cardiosympathetic regulation through the M3 R on the orexin neurons that directly project to the RVLM.
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yu-Wen E
authors.initials: YW
authors.lastname: Dai
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yen-Hsien
authors.initials: YH
authors.lastname: Lee
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Jennifer Y S
authors.initials: JY
authors.lastname: Chen
authors.affiliation: Biostatistic Center, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yen-Kuang
authors.initials: YK
authors.lastname: Lin
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Department of Physiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Hwang
mesh_terms: D000818:Animals; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000378:metabolism*; D009434:Neural Pathways; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D000068797:Orexins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043587:Receptor, Muscarinic M3 / Q000378:metabolism*
chemical_list: D000068797:Orexins; D043587:Receptor, Muscarinic M3
keywords: M3; RVLM; hypocretin; muscarinic receptor; orexin