title: Conserved expression of the GPR151 receptor in habenular axonal projections of vertebrates.
abstract: 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.
authors.affiliation: Psychiatric Neuromodulation Unit, Clinical Sciences, Lund University, 222 42, Lund, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Broms
authors.forename: Beatriz
authors.initials: B
authors.lastname: Antolin-Fontes
authors.forename: Anders
authors.initials: A
authors.lastname: Tingström
authors.forename: Ines
authors.initials: I
authors.lastname: Ibañez-Tallon
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D019262:Habenula / Q000166:cytology*; D006801:Humans; D066268:Interpeduncular Nucleus / Q000502:physiology; D008636:Mesencephalon / Q000033:anatomy & histology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009415:Nerve Net / Q000378:metabolism*; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D018013:Receptors, Neuropeptide / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity; D013373:Substance P / Q000378:metabolism; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014714:Vertebrates / Q000033:anatomy & histology / Q000378:metabolism; D050496:Vesicular Glutamate Transport Proteins / Q000378:metabolism; D015027:Zebrafish; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: D016900:Neurofilament Proteins; C485721:Npbwr1 protein, mouse; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D050496:Vesicular Glutamate Transport Proteins; C051774:neurofilament protein H; D013373:Substance P; D014446:Tyrosine 3-Monooxygenase; D014365:Tryptophan Hydroxylase; D002795:Choline O-Acetyltransferase; D001616:beta-Galactosidase
keywords: AB_10123643; AB_10608138; AB_10743815; AB_2079751; AB_261587; AB_307210; AB_477560; AB_572266; AB_628299; AB_887876; AB_887878; AB_887883; AB_887884; AB_90754; G protein-coupled receptor; MGI_MGI:3606630; RGD_737929; SciRes_000137; ZIRC_ZL1; fasciculus retroflexus; interpeduncular nucleus; raphe nucleus; rhabdoid nucleus; rostromedial tegmental nucleus