Non-canonical GABAergic Pathways in the Visual System

项目总结 光对各种生物体的生理和行为都起着极其重要的调节作用。 光信息通过视网膜神经节细胞释放的谷氨酸从视网膜传递到大脑 40多个大脑区域的视网膜节细胞(RGC)，一些视网膜节细胞还共同释放多肽递质。尽管 尽管普遍认为所有的视网膜节细胞都会释放谷氨酸，但有迹象表明，一些视网膜节细胞可能是GABA能的。 然而，这些潜在的GABA能RGC的身份和功能是完全未知的。我们最近 研究结果表明，表达黑素的、固有的光敏(IP)RGC的一部分是 伽巴气体。这一提议将检验GABA从黑素释放的首要假设-- 表达固有的光敏(IP)RGC会影响非成像行为。这样做的目的是 提案将定义GABA能RGC的类型和目标，以及它们在视觉行为中的作用 结合小鼠遗传学、基于通道视紫质的电路追踪、解剖学、膜片钳 电生理学和行为学。除了绘制GABA能RGC的身份和功能图外，这些 研究将开辟新的研究领域，研究抑制电路在光驱动行为和 生理学。

PROJECT SUMMARY Light is a profoundly important regulator of physiology and behavior across a wide range of organisms. Light information is relayed from the retina to the brain via glutamate released from retinal ganglion cells (RGCs) at more than 40 brain regions, with some RGCs also co-releasing peptide transmitters. Despite the prevailing dogma that all RGCs release glutamate, there have been hints that some RGCs may be GABAergic. However, the identity and function of these potentially GABAergic RGCs is completely unknown. Our recent findings indicate that a subset of the melanopsin-expressing, intrinsically photosensitive (ip)RGCs are GABAergic. This proposal will test the overarching hypothesis that GABA release from the melanopsin- expressing, intrinsically photosensitive (ip)RGCs influences non-image forming behaviors. The aims of this proposal will define the types and targets of GABAergic RGCs and their role in visual behavior using a combination of mouse genetics, channelrhodopsin-based circuit tracing, anatomy, patch clamp electrophysiology, and behavior. In addition to mapping the identity and function of GABAergic RGCs, these studies will open up new areas of research into the role of inhibitory circuits in light-driven behavior and physiology.