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沿首选方向移动的图像反应强烈，对沿相反方向或零方向移动的图像反应较弱，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，稳定视网膜上的图像。方向选择性神经节细胞的首选方向沿着基本方向（上、下、左、右）聚集，并且对每个基本方向敏感的方向选择性神经节细胞被组织成马赛克，使得在空间中的每个点处，代表每个运动方向。视网膜中产生方向选择性的主要模型是一类特定的中间神经元在方向选择性神经节细胞树突树的无效侧形成抑制性突触。指示由在发育过程中接收不对称分布的抑制输入的细胞组成的嵌合体出现的机制尚不清楚。 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发展背后的机制——零侧抑制背后的电路和方向选择性神经节细胞镶嵌体的存在。特别是，我们将确定自发的视网膜活动是否在这些回路的形成中发挥关键作用。 公共健康相关性：我们的研究目标是确定指导哺乳动物视网膜视觉反应发展的因素。特别是，我们正在研究视网膜检测视觉场景中物体运动方向能力的电路。这种“方向选择性”对于正常的视觉驱动反射至关重要，当我们在视觉场景中移动时，它可以稳定视网膜上的图像。我们的工作将确定视网膜中的神经活动在这些方向选择电路的连接中发挥什么作用。详细了解控制神经回路正常发育的组织原则可能有助于了解神经出生缺陷的起源。在发育的早期，在视觉体验成为可能之前，整个不成熟的视觉系统会自发产生电和化学活动。越来越多的证据表明，这种早期活动对于介导视觉的回路的适当发育至关重要。这些发现让我们深入了解为什么胎儿接触药物会导致多种神经病理学。此外，深入了解神经活动的作用将为制定策略提供重要见解，使神经系统能够重新连接正常功能的神经回路，以应对影响视力的发育异常。

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.