GPR151 is a G-protein coupled receptor for which the endogenous ligand remains 
unknown. In the nervous system of vertebrates, its expression is enriched in 
specific diencephalic structures, where the highest levels are observed in the 
habenular area. The habenula has been implicated in a range of different 
functions including behavioral flexibility, decision making, inhibitory control, 
and pain processing, which makes it a promising target for treating psychiatric 
and neurological disease. This study aimed to further characterize neurons 
expressing the Gpr151 gene, by tracing the afferent connectivity of this 
diencephalic cell population. Using pseudotyped rabies virus in a transgenic 
Gpr151-Cre mouse line, monosynaptic afferents of habenular and thalamic 
Gpr151-expressing neuronal populations could be visualized. The habenular and 
thalamic Gpr151 systems displayed both shared and distinct connectivity 
patterns. The habenular neurons primarily received input from basal forebrain 
structures, the bed nucleus of stria terminalis, the lateral preoptic area, the 
entopeduncular nucleus, and the lateral hypothalamic area. The Gpr151-expressing 
neurons in the paraventricular nucleus of the thalamus was primarily contacted 
by medial hypothalamic areas as well as the zona incerta and projected to 
specific forebrain areas such as the prelimbic cortex and the accumbens nucleus. 
Gpr151 mRNA was also detected at low levels in the lateral posterior thalamic 
nucleus which received input from areas associated with visual processing, 
including the superior colliculus, zona incerta, and the visual and 
retrosplenial cortices. Knowledge about the connectivity of Gpr151-expressing 
neurons will facilitate the interpretation of future functional studies of this 
receptor.