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

J Comp Neurol. 2013 Jul 1;521(10):2208-34. doi: 10.1002/cne.23273.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain / anatomy & histology
  • Brain / metabolism
  • Cell Count
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics*
  • Hypothalamus / cytology*
  • Hypothalamus / metabolism*
  • Leptin / pharmacology
  • Luminescent Proteins / genetics
  • Mice
  • Mice, Transgenic
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neurons / chemistry*
  • Neurons / classification
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neuropeptide Y / metabolism
  • Neuropeptides / metabolism
  • Pro-Opiomelanocortin / genetics
  • Pro-Opiomelanocortin / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Somatostatin / genetics
  • Receptors, Somatostatin / metabolism*


  • Leptin
  • Luminescent Proteins
  • Mchr1 protein, mouse
  • Nerve Tissue Proteins
  • Neuropeptide Y
  • Neuropeptides
  • RNA, Messenger
  • Receptors, Somatostatin
  • Pro-Opiomelanocortin