Development of direction selectivity in retina

描述（由申请人提供）：方向选择性神经节细胞对向首选方向移动的图像反应强烈，对向相反方向或零方向移动的图像反应弱，并且对于驱动眼运动反射至关重要，当我们在视觉场景中移动时，眼运动反射稳定视网膜上的图像。方向选择神经节细胞的首选方向沿着基本方向（上、下、左、右）聚集，对每个基本方向敏感的方向选择神经节细胞被组织成马赛克，这样在空间的每个点上，每个运动方向都被表示出来。在视网膜中产生方向选择性的主要模型是一类特殊的中间神经元在方向选择性神经节细胞树突状树的空侧形成抑制性突触。在发育过程中，由接受不对称抑制输入的细胞组成的嵌合体的机制尚不清楚。在这里，我们建议结合使用最先进的电生理学和成像技术来确定方向选择性这两个基本特征的发展机制——零侧抑制和方向选择性神经节细胞嵌合存在的基础电路。特别是，我们将确定自发视网膜活动是否在这些电路的形成中起关键作用。

DESCRIPTION (provided by applicant): 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, and are critical for driving ocular-motor reflexes that stabilize images on the retina as we move through a visual scene. The preferred direction of direction-selective ganglion cells cluster along the cardinal directions (up, down, left and right) and the direction-selective ganglion cells sensitive to each cardinal direction are organized into mosaics such that at each point in space, each direction of motion is represented. The predominant model for the generation of direction selectivity in the retina is that a particular class of interneurons forms inhibitory synapses on the null side of the dendritic tree of direction- selective ganglion cells. The mechanisms that instruct the emergence of mosaics comprised of cells that receive an asymmetric distribution of inhibitory inputs during development are unknown. Here we propose to use a combination of state-of-the-art electrophysiological and imaging techniques to determine the mechanisms that underlie the development of these two essential features of direction-selectivity - the circuits that underlie the null side inhibition and the existence of direction-selective ganglion cells mosaics. In particular, we will determine whether spontaneous retinal activity plays a critical role in the formation of these circuits. PUBLIC HEALTH RELEVANCE: Our research goal is to determine the factors that instruct the development of visual responses in the mammalian retina. In particular, we are studying the circuits that underlie the ability of the retina to detect the direction of motion of an object in the visual scene. This "direction-selectivity" is critical for the normal visually-driven reflexes that stabilize an image on the retina as we move through a visual scene. Our work will determine what role neural activity in the retina plays in the wiring up of these direction-selective circuits. Developing a detailed understanding of the organizing principles that govern the normal development of the circuits may make it possible to understand the origin of neurological birth defects. Very early in the development, before visual experience is possible, both electrical and chemical activity is generated spontaneously throughout the immature visual system. There is growing evidence that this early activity is critical for the appropriate development of circuits that mediate vision. These findings give us insights as to why exposure of fetuses to pharmacological agents can lead to a variety of neuropathologies. In addition, gaining insights into the role of neural activity will provide critical insights into devising strategies that allow the nervous system to rewire normal functioning neural circuits in response to developmental abnormalities that affect vision.