Anatomical and Neuronal Distribution of the G‐Coupled Protein Receptor 75 mRNA in the Mouse Central Nervous System

G-protein coupled receptor (GPCR) 75 (GPR75) is a 540 amino acid member of the G_αq class of GPCRs, with no homology with other classic GPCRs. The current focus on GPR75 has centred on its potential role in metabolic disorders and cancer. GPR75 expression is abundant in the central nervous system (CNS) more so than in the peripheral tissues; however, much remains unknown about the distribution and role of this receptor throughout the CNS. In this study, we quantified GPR75 mRNA expression in the mouse CNS using RNAscope fluorescent in situ hybridization (FISH) technology, combined with immunohistochemistry (IHC) to detect GPR75 transcripts in specific neuronal cell types. GPR75 knockout (KO) mice were used as controls and specificity of hybridization. Our results show that GPR75 mRNA expression occurs in several neuronal populations including GABAergic and glutamatergic neurons. In select areas, such as the substantia nigra/ventral tegmental area, locus coeruleus and raphe nucleus, GPR75 mRNA is also highly expressed in monoaminergic neurons. Moreover, we found high expression of GPR75 mRNA in the cerebellum, in both GABAergic and glutamatergic neurons, suggesting a potential role for this receptor in motor/equilibrium activity. Indeed, GPR75 KO mice perform significantly better than wild-type littermates on the rotarod test. Our data suggest that this receptor may play an important role in brain physiology and function.