Spatial distribution of melanin-concentrating hormone receptor 1 in the ventral tegmental area

Abstract

Melanin-concentrating hormone (MCH) activates MCH receptor 1 (MCHR1) to promote positive energy balance. MCH or MCHR1 deletion, in part at GABAergic cells, leads to a hyperdopaminergic state and hyperactivity, as MCH can inhibit dopamine release. Here we assessed if MCH can directly regulate dopaminergic or GABAergic neurons in the ventral tegmental area (VTA). We labelled mouse Mchr1 mRNA by RNAscope in situ hybridization throughout the VTA and quantified its expression on putative dopaminergic or GABAergic cells by colocalization with tyrosine hydroxylase (TH) immunoreactivity or Slc32a1 (Vgat) mRNA hybridization, respectively. Half of all Mchr1 cells expressed TH, which comprised 25% of TH VTA cells, while only 13% of Mchr1 cells expressed Vgat, which represented 13% of Vgat VTA cells. We then mapped the expression of Mchr1 in TH and Vgat VTA neurons onto Allen Reference Atlas brain templates to assess their spatial distribution. Mchr1 expression was most prevalent in the posterior VTA (Bregma -3.28 mm to -3.68 mm) and concentrated within the medial aspect of the VTA. Vgat expression and its colocalization with Mchr1 increased in more posterior levels but TH and Mchr1 colocalization was relatively higher posteriorly. Interestingly, 36% of Mchr1 cells were neither TH nor Vgat positive, and future experiments will determine if they may be glutamatergic VTA cells. Importantly, we provide evidence for Mchr1 expression in the VTA and provide the basis for electrophysiological recordings to assess MCH-mediated action at TH and Vgat VTA cells.