Characterization of Melanin-Concentrating Hormone Cells Coexpressing Cocaine- and Amphetamine-Regulated Transcript

Melanin-concentrating hormone (MCH) is a neuropeptide produced almost exclusively in the lateral hypothalamus.MCH cells regulate many behaviours including feeding, sleep, stress, cognition, and maternal behaviour.There are also subpopulations of MCH cells that are neurochemically distinct, which could underlie the functional diversity of this cell type.Notably, about half of MCH cells coexpress cocaine-and amphetamine-regulated transcript (CART).CART influences many of the same behaviours as MCH, but these two peptides often act in opposition.For example, MCH promotes feeding and positive energy balance, but CART can be either orexigenic or anorexigenic.The unique roles of MCH/CART+ and MCH/CART-cells are not known, but these neurochemically distinct subpopulations could contribute to distinct behaviours.To help define their roles in MCH-related neuronal networks, we defined the neuroanatomical, electrical, and morphological properties of MCH/CART+ and MCH/CART-cells in male and female mice.First, we made spatial maps of the distribution of CART in MCH cells and found that MCH/CART+ and MCH/CART-cells were anatomically divided.Second, we analyzed the electrical activity and structure of each cell type and found differences in their excitability and response to stimulation.Third, we traced their dendritic structure and found that male MCH/CART+ were highly branched.These results highlight variations in the regulation of each MCH cell subtype and suggest that they could be implicated in different cellular networks.This work will help resolve the complexity of the MCH system by characterizing MCH/CART+ and MCH/CART-cells that could underpin the diverse functions of MCH neurons.