Mapping GPR88-Venus illuminates a novel role for GPR88 in sensory processing.
Mapping GPR88-Venus illuminates a novel role for GPR88 in sensory processing.
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DOI：
10.1007/s00429-017-1547-3
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发表时间：
2018-04
影响因子：
3.1
通讯作者：
Kieffer BL
中科院分区：
文献类型：
--
作者：
Ehrlich AT;Semache M;Bailly J;Wojcik S;Arefin TM;Colley C;Le Gouill C;Gross F;Lukasheva V;Hogue M;Darcq E;Harsan LA;Bouvier M;Kieffer BL
GPR 88是一种孤儿G蛋白偶联受体，最初以纹状体富集的转录物为特征，是神经精神疾病的潜在靶点。目前，在小鼠中的基因敲除研究基本上集中在纹状体相关的功能和GPR 88蛋白在大脑中的分布和功能的全面知识仍然缺乏。在这里，我们首先创建了表达功能性荧光受体的Gpr 88-Venus敲入小鼠，以精细绘制GPR 88在大脑中的定位。在神经元索马、纤维和初级纤毛中检测到受体蛋白，这取决于大脑区域，值得注意的是，全脑映射显示了尚未报道的第4层皮质分层模式，特别是在感觉处理区。在L4的体感皮层的独特的桶图案出现在出生后3天，并持续到成年，这表明在感觉统合的潜在功能的GPR 88。接下来，我们检查了Gpr 88基因敲除小鼠在感觉任务中的皮质结构和行为反应。活体小鼠的磁共振成像显示异常高的各向异性分数，主要在躯体感觉皮层和尾壳核，表明这些GPR 88富集区的显着微结构改变。此外，行为分析显示，延迟响应的体感，视觉和嗅觉依赖的任务，证明了GPR 88的作用，而不是感知的感官刺激的整合。总之，我们的数据首次显示了GPR 88在多感觉处理中的重要作用。由于感觉整合在许多精神疾病中被破坏，我们的研究明确地将GPR 88定位为治疗精神障碍的靶点，可能通过皮层感觉网络的活动。
GPR88 is an orphan G-protein coupled receptor originally characterized as a striatal-enriched transcript and is a potential target for neuropsychiatric disorders. At present, gene knockout studies in the mouse have essentially focused on striatal-related functions and a comprehensive knowledge of GPR88 protein distribution and function in the brain is still lacking. Here, we first created Gpr88-Venus knock-in mice expressing a functional fluorescent receptor to fine-map GPR88 localization in the brain. The receptor protein was detected in neuronal soma, fibers and primary cilia depending on the brain region, and remarkably, whole-brain mapping revealed a yet unreported layer-4 cortical lamination pattern specifically in sensory processing areas. The unique GPR88 barrel pattern in L4 of the somatosensory cortex appeared three days after birth and persisted into adulthood, suggesting a potential function for GPR88 in sensory integration. We next examined Gpr88 knockout mice for cortical structure and behavioral responses in sensory tasks. Magnetic resonance imaging of live mice revealed abnormally high fractional anisotropy, predominant in somatosensory cortex and caudate putamen, indicating significant microstructural alterations in these GPR88-enriched areas. Further, behavioral analysis showed delayed responses in somatosensory-, visual- and olfactory-dependent tasks, demonstrating a role for GPR88 in the integration rather than perception of sensory stimuli. In conclusion, our data show for the first time a prominent role for GPR88 in multisensory processing. Because sensory integration is disrupted in many psychiatric diseases, our study definitely positions GPR88 as a target to treat mental disorders perhaps via activity on cortical sensory networks.
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影响因子：
3.3
作者：
Gardon, O.;Faget, L.;Chung, P. Chu Sin;Matifas, A.;Massotte, D.;Kieffer, B. L.
通讯作者：
Kieffer, B. L.
影响因子：
2.7
作者：
Dzierba, Carolyn D.;Bi, Yingzhi;Macor, John E.
通讯作者：
Macor, John E.
影响因子：
15.9
作者：
Cudeiro, Javier;Sillito, Adam M.
通讯作者：
Sillito, Adam M.
影响因子：
3.3
作者：
Ghate, A.;Befort, K.;Kieffer, B. L.
通讯作者：
Kieffer, B. L.
影响因子：
16.2
作者：
Ferezou, Isabelle;Haiss, Florent;Petersen, Carl C. H.
通讯作者：
Petersen, Carl C. H.