Neurochemical characterization of neurons expressing melanin- concentrating hormone receptor 1 in the mouse hypothalamus

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Melanin- concentrating hormone (MCH) is a hypothalamic neuropeptide that acts via MCH receptor 1 (MCHR1) in the mouse. It promotes positive energy balance; thus, mice lacking MCH or MCHR1 are lean, hyperactive, and resistant to diet- induced obesity. Identifying the cellular targets of MCH is an important step to understanding the mechanisms underlying MCH actions. We generated the Mchr1- cre mouse that expresses cre recombinase driven by the MCHR1 promoter and crossed it with a tdTomato reporter mouse. The resulting Mchr1- cre/tdTomato progeny expressed easily detectable tdTomato fluorescence in MCHR1 neurons, which were found throughout the olfactory system, striatum, and hypothalamus. To chemically identify MCH- targeted cell populations that play a role in energy balance, MCHR1 hypothalamic neurons were characterized by colabeling select hypothalamic neuropeptides with tdTomato fluorescence. TdTomato fluorescence colocalized with dynorphin, oxytocin, vasopressin, enkephalin, thyrothropin- releasing hormone, and corticotropin- releasing factor immunoreactive cells in the paraventricular nucleus. In the lateral hypothalamus, neurotensin, but neither orexin nor MCH neurons, expressed tdTomato. In the arcuate nucleus, both Neuropeptide Y and proopiomelanocortin cells expressed tdTomato. We further demonstrated that some of these arcuate neurons were also targets of leptin action. Interestingly, MCHR1 was expressed in the vast majority of leptin- sensitive proopiomelanocortin neurons, highlighting their importance for the orexigenic actions of MCH. Taken together, this study supports the use of the Mchr1- cre mouse for outlining the neuroanatomical distribution and neurochemical phenotype of MCHR1 neurons. J. Comp. Neurol. 521:2208– 2234, 2013. © 2012 Wiley Periodicals, Inc.Melanin- concentrating hormone (MCH) is an orexigenic neuropeptide that acts on MCH receptors 1 (MCHR1) in rodents. This study uses the Mchr1- cre/tdTomato mouse to readily identify MCHR1- expressing neurons by red fluorescence. We found that MCHR1 is expressed in different cell types throughout the hypothalamus. Thus we provide a neuroanatomical basis for MCH to regulate neuroendocrine and autonomic functions, including energy balance and appetite.

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