title: Melanin-concentrating hormone inputs to the nucleus accumbens originate from distinct hypothalamic sources and are apposed to GABAergic and cholinergic cells in the Long-Evans rat brain.
abstract: Melanin-concentrating hormone [MCH] is a neuropeptide that modulates several behaviors, such as feeding and reward. Because the hedonic and rewarding features of a food also influence feeding behavior, the nucleus accumbens [Acb] has been highlighted as a key area integrating these roles. Functional data confirm that MCH acts on a subdivision of the Acb; however, considering the importance of finding anatomical and neurochemical data that correlate the previously demonstrated function of MCH, we delineated this investigation based on the following points: (1) Is there a pattern of innervation by MCH fibers regarding the subregions within the Acb? (2) Specifically, which hypothalamic nuclei synthesize MCH and innervate the Acb? (3) Finally, what are the neurochemical identities of the accumbal neurons innervated by MCH inputs? We examined the MCH immunoreactivity [MCH-ir] in the Acb in rat brains using the peroxidase technique. Additionally, after injecting retrograde neuronal tracer [Fluoro-Gold® - FG®] into subdivisions of the Acb [shell or core], we mapped single- or double-labeled cells. Moreover, using a double immunoperoxidase protocol, we investigated the MCH-ir fibers for gamma-aminobutyric acid [GABA]-ir and choline acetyltransferase [ChAT]-ir cells in the shell subdivision of the Acb [AcbSh]. We found that the MCH-ir fibers preferentially innervate the medial AcbSh, particularly the septal pole. This innervation originated from the incerto-hypothalamic area [IHy], internuclear area, lateral hypothalamic area, perifornical area, periventricular nucleus and posterior hypothalamus. Moreover, the IHy has the highest relationship between double/single retrogradely labeled cells [n=5.33±0.66/16±0.93, i.e. 33.33%] in the whole hypothalamus. Furthermore, our data suggest that MCH-ir fibers are in apposition to GABAergic and cholinergic cells in the AcbSh. Therefore, we provide anatomical support to the ongoing functional studies investigating the relation among the hypothalamus, MCH transmission into the Acb and the involvement of known neuronal phenotypes within the AcbSh.
authors.affiliation: Laboratory of Chemical Neuroanatomy, Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, Brazil. Electronic address: carlos.haemmerle@gmail.com.
authors.forename: C A S
authors.initials: CA
authors.lastname: Haemmerle
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, Brazil. Electronic address: aninha@icb.usp.br.
authors.forename: A M P
authors.initials: AM
authors.lastname: Campos
authors.affiliation: Laboratory of Chemical Neuroanatomy, Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, Brazil; Center for Neuroscience and Behavior, Institute of Psychology, University of São Paulo, 05508-000 São Paulo, Brazil. Electronic address: jcbitten@icb.usp.br.
authors.forename: J C
authors.initials: JC
authors.lastname: Bittencourt
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002452:Cell Count; D005455:Fluorescent Antibody Technique; D007028:Hypothalamic Hormones / Q000378:metabolism*; D007031:Hypothalamus / Q000166:cytology* / Q000378:metabolism; D007124:Immunoenzyme Techniques; D008297:Male; D008543:Melanins / Q000378:metabolism*; D056347:Neuroanatomical Tract-Tracing Techniques; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D009714:Nucleus Accumbens / Q000166:cytology* / Q000378:metabolism; D010784:Photomicrography; D010907:Pituitary Hormones / Q000378:metabolism*; D020318:Rats, Long-Evans; D013266:Stilbamidines; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D007028:Hypothalamic Hormones; D008543:Melanins; D010907:Pituitary Hormones; D013266:Stilbamidines; D005680:gamma-Aminobutyric Acid; C019463:melanin-concentrating hormone; D000109:Acetylcholine
keywords: feeding behavior; food reward; incerto-hypothalamic area; lateral hypothalamic area; motivated behavior; nucleus accumbens connections