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, and is 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 protein-coupled 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 
patterns were 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.