Broms Jonas, Grahm Matilda, Haugegaard Lea, Blom Thomas, Meletis Konstantinos, Tingström Anders
Psychiatric Neuromodulation Unit, Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden.
Biomedical Services Division, Faculty of Medicine, Lund University, Lund, Sweden.
J Comp Neurol. 2017 Oct 15;525(15):3227-3250. doi: 10.1002/cne.24273. Epub 2017 Jul 24.
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.
GPR151是一种G蛋白偶联受体，其内源性配体尚不清楚。在脊椎动物的神经系统中，它在特定的间脑结构中表达丰富，其中在缰核区域观察到最高水平。缰核涉及一系列不同的功能，包括行为灵活性、决策、抑制控制和疼痛处理，这使其成为治疗精神疾病和神经疾病的一个有前景的靶点。本研究旨在通过追踪这个间脑细胞群的传入连接，进一步表征表达Gpr151基因的神经元。在转基因Gpr151-Cre小鼠品系中使用假型狂犬病病毒，可以可视化缰核和丘脑表达Gpr151的神经元群体的单突触传入。缰核和丘脑的Gpr151系统显示出共同和不同的连接模式。缰核神经元主要接受来自基底前脑结构、终纹床核、外侧视前区、内囊核和外侧下丘脑区的输入。丘脑室旁核中表达Gpr151的神经元主要与下丘脑内侧区域以及未定带接触，并投射到特定的前脑区域，如前边缘皮层和伏隔核。在丘脑外侧后核中也检测到低水平的Gpr151 mRNA，该核接受来自与视觉处理相关区域的输入，包括上丘、未定带以及视觉和压后皮层。了解表达Gpr151的神经元的连接性将有助于解释该受体未来的功能研究。
