撤光型方向选择性视网膜神经节细胞J-RGC的环路机制

Direction selective circuit is one of the most widely studied neural circuits in the retina. For a long time, it's believed that there are only two types of direction selective ganglion cells (DSGC) in the mammalian retina, the ON DSGCs and the ON-OFF DSGCs. Previous work of the applicant discovered a novel type of OFF DSGCs in the mouse retina, the J-RGCs, and found they likely rely on different mechanisms for their direction selectivity than the known ones. Taking advantages of the available transgenic mouse lines, combining the traditional electrophysiological tools such as patch clamp recording and the cutting edge molecular genetics techniques such as optogetics interrogation of neural circuits, this proposal aims to decipher the synaptic and circuit mechanisms underlying the generation of direction selectivity in the J-RGCs. The specific aims are: 1) Locate the origin of direction selectivity in the J-RGC circuit. 2). Determine the synaptic mechanism through which the direction selectivity arises. 3) Using the new circuit mapping techniques, discover circuit components, and elucidate the roles each member of the J-RGC circuit plays in the generation of direction selectivity. 4) Study the relationship between J-RGC's asymmetric structure and its function. The proposed research will help understand the different strategies through which the nervous system gives rise to direction selectivity.

方向选择性环路是被最广泛研究的视网膜神经环路之一。长期以来认为哺乳动物视网膜中有两种方向选择性神经节细胞（DSGC），给光型和给光-撤光型。本项目负责人的前期研究在小鼠视网膜中发现了一种新型的撤光型的方向选择性神经节细胞J-RGC, J-RGC方向选择性的产生有可能是通过一个新型的机制。本项目将利用已有的转基因小鼠资源，有机结合膜片钳等传统的电生理方法及光遗传等先进的分子遗传技术，对J-RGC方向选择性的突触及环路机理进行研究，以期1)确定方向选择性在J-RGC环路中首次出现的部位。2)揭示方向选择性在J-RGC环路上述部位产生的机制。3)应用新的环路研究手段，阐述J-RGC环路的组成，及环路成员在方向选择性中起到的作用。4)解答J-RGC的结构与功能之间的关系。最终增强对方向选择性在神经系统中产生的各种不同机制的理解。