Development of direction selectivity in retina

项目总结--与父级奖励不变 神经回路的发展涉及分子线索和神经活动之间的丰富相互作用。这是 可能在视觉系统中研究得最好，在视觉系统中，几种分子相互作用已被确定为 对于早期建立粗略的视觉地图至关重要，而早期的自发活动称为视网膜 睁眼前的波和睁眼后的视觉剥夺会导致地图精细化。 我们在视网膜的一个方向选择性神经节细胞中研究这个问题。定向选择性神经节细胞 对沿优选方向移动的图像响应强烈而对沿相反方向移动的图像响应弱， 或空方向。方向选择性神经节细胞对于驱动稳定的眼球运动反射至关重要 当我们在视觉场景中移动时，视网膜上的图像以及用于感知内部对象移动的图像 视觉场景。方向选择性神经节细胞的优先方向沿以下四个方向聚集 沿着两个光流轴排列，我们称之为方向选择性图。其作用机制 指导这一方向选择性图谱发展的因素是未知的。 在这里，我们建议使用最先进的双光子钙成像、电生理学和 转基因小鼠策略，以确定发展方向的基础机制 选择性地图。特别是，我们将确定神经信号，无论是通过缝隙连接还是视网膜波， 在这些方向选择性图的形成中起着关键作用。最后，我们将测试候选突触 在rna-seq屏幕上发现的可能指示功能性抑制性突触出现的分子。 这是方向选择性反应的基础。

PROJECT SUMMARY -- NO CHANGE FROM PARENT AWARD The development of neural circuits involves a rich interplay between molecular cues and neural activity. This is perhaps most well studied in the visual system, where several molecular interactions have been identified as being critical for early establishment of coarse visual maps while both early spontaneous activity called retinal waves prior to eye opening and visual deprivation after eye opening leads to map refinement. We study this question in a direction-selective ganglion cells of the retina. Direction selective ganglion cells respond strongly to an image moving in the preferred direction and weakly to an image moving in the opposite, or null direction. Direction-selective ganglion cells are critical for driving ocular-motor reflexes that stabilize images on the retina as we move through a visual scene as well as for sensing the movement of objects within the visual scene. The preferred directions of direction selective ganglion cells cluster along four directions that align along two optic flow axes, an organization we refer to as the direction selectivity map. The mechanisms that instruct the development of this direction selectivity map are unknown. Here we propose to use a combination of state-of-the-art two-photon calcium imaging, electrophysiology, and transgenic mouse strategies to determine the mechanisms that underlie the development of the direction selectivity maps. In particular, we will determine if neural signaling, either through gap junctions or retinal waves, play a critical role in the formation of these direction selectivity maps. Finally, we will test candidate synaptogenic molecules identified in an RNA-seq screen that may instruct the emergence of the functional inhibitory synapses that underlie direction selective responses.