Melanin-concentrating hormone receptor-1 is located in primary cilia of the dorsal raphe neurons

The melanin-concentrating hormone (MCH) is a peptidergic neuromodulator synthesized by neurons of the posterior hypothalamus and incerto-hypothalamic area. These neurons project throughout the central nervous system, including the dorsal raphe nucleus (DRN). In rodents, MCH exerts its biological functions through the MCHR-1 receptor. We previously demonstrated that infra-DRN MCH administration increases REM sleep time and induces a pro-depressive behavior. We also determined that MCH modulates the neuronal firing rate and serotonin release within this nucleus. Previous studies in mice identified the presence of MCHR-1 in neurons located in the olfactory tubercle, hypothalamus, and nucleus accumbens, in a specialized neuronal appendage: the neuronal primary cilia. However, the subcellular location of MCHR-1 protein in the DRN is still unknown. Hence, the aim of the present study was to explore, by means of single and double immunohistochemical procedures, whether MCHR-1 is present in neuronal primary cilia in serotonergic and GABAergic neurons located in the DRN of the rat. We demonstrated colocalization of MCHR-1 with type III adenylyl cyclase (AC-III), a neuronal ciliary marker, in the DRN and confirmed their colocalization in the hippocampus and cerebral cortex of the rat. We quantified the proportion of serotoninergic and GABAergic neurons that coexpress MCHR-1 at the mid-caudal and mid-rostral levels of the DRN: 4% and 12%, respectively. Furthermore, approximately 10% of the total number of MCHR-1 immunoreactive primary cilia belonged to serotonergic neurons, whilst 12% were appendages of GABAergic neurons. These morphological data allow us to conclude that the mechanism by which MCH modulates the activity of DRN neurons is through MCHR-1 receptors present in the primary cilia of different neurochemical phenotypes. New experiments are needed to understand the functional rationale of the unexpected localization of these receptors and to explore their presence in other neuronal phenotypes.