Conserved expression of the GPR151 receptor in habenular axonal projections of vertebrates.

The habenula is a phylogenetically conserved brain structure in the epithalamus. It is a major node in the information flow between fronto-limbic brain regions and monoaminergic brainstem nuclei, thus anatomically and functionally ideally positioned to regulate emotional, motivational and cognitive behaviors. Consequently, the habenula may be critically important in the pathophysiology of psychiatric disorders such as addiction and depression. Here we investigated the expression pattern of GPR151, a G coupled-protein receptor (GPCR), whose mRNA has been identified as highly and specifically enriched in habenular neurons by in situ hybridization and Translating Ribosome Affinity Purification (TRAP). In the present immunohistochemical study we demonstrate a pronounced and highly specific expression of the GPR151 protein in the medial and lateral habenula of rodent brain. Specific expression was also seen in efferent habenular fibers projecting to the interpeduncular nucleus, the rostromedial tegmental area, the rhabdoid nucleus, the mesencephalic raphe nuclei and the dorsal tegmental nucleus. Using confocal microscopy and quantitative colocalization analysis we found that GPR151 expressing axons and terminals overlap with cholinergic, substance P-ergic and glutamatergic markers. Virtually identical expression pattern was observed in rat, mouse and zebrafish brains. Our data demonstrate that GPR151 is highly conserved, specific for a subdivision of the habenular neurocircuitry, and constitutes a promising novel target for psychiatric drug development. J. Comp. Neurol., 2014. © 2014 Wiley Periodicals, Inc