Monosynaptic retrograde tracing of neurons expressing the G‐protein coupled receptor Gpr151 in the mouse brain

Abstract

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.

Gene expression profiles complement the analysis of genomic modifiers of the clinical onset of Huntington disease

“…39 Furthermore, functional characterization of neuronal Gpr151 suggested that the gene is important in the paraventricular nucleus and could therefore be potentially implicated in food and drug seeking behaviors. 40 Future studies should therefore aim at delineating the potential role of serotonin, glucocorticoids and these two orphan GPCRs with regards to metabolic dysfunction observed in HD, in relation to modifying age of onset of the disorder.…”

Ab Initio Modelling the Structure of Proton-Sensing G-Protein Coupled Receptor GPR151

“…Yet, in the NCBI database, the number of experimentally identified protein sequences is in great excess of that of experimentally determined protein structures inside the almost-half-a-century old PDB [1]. For instance, GPR151 is an proton-sensing G-protein coupled receptor (GPCR) originally identified as homologous to galanin receptors [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30].…”

Study of the DiI method accuracy on the example of the afferent connections of the Habenula in P6 F1-C57Bl6 / CBA mice

“…A particular problem is the fact that even for Hb, which connections are well described for rats, there is still no complete scheme of afferent connections for mice described in the literature, despite a number of qualitative studies already done (Qin C, Luo M, 2009;Broms J et al, 2017). In other words, there is some (very low) probability that mice's MHb can be associated with LPA, and mice's LHb with TS and SFi.…”

“…The best way to investigate DiI injection for accuracy, it to test already known brain structures, whose connections are well described, for example, on Habenula (Hb). Hb is a paired structure of the intermediate brain, its afferent connections are described in detail in the literature both for rats (Herkenham M, Nauta WJ, 1977) and partially for mice (Qin C, Luo M. 2009;Broms J et al, 2017). It is known that Medial Habenular nuclei (MHb) is innervated by Septum nuclei, such as Triangular septal nuclei (TS) and Septofimbrial septal nuclei (SFi); Lateral Habenular nuclei is innervated by the Lateral pteoptic area (LPA).…”

“…Originally this work was planned as a test of this particular assumption. The scheme of the connections of different Hb nuclei with forebrain structures is described in details in the literature both for rats (Herkenham M, Nauta WJ, 1977) and partially for mice (Qin C, Luo M, 2009;Broms J et al, 2017). It is known that LHb is connected by afferent onesided connections with LPA, MHb is connected by afferent one-way connections with TS and SFi.…”