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在优选方向上移动的图像响应强烈，而对在相反或零方向上移动的图像响应微弱，并且对于驱动眼运动反射至关重要，所述眼运动反射在我们移动通过视觉场景时稳定视网膜上的图像。方向选择性神经节细胞的优选方向沿着基本方向（上、下、左和右）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，每个运动方向都被表示。在视网膜中产生方向选择性的主要模型是特定类别的中间神经元在方向选择性神经节细胞的树突树的无效侧上形成抑制性突触。指示马赛克的出现的机制是未知的，马赛克由在发育过程中接受抑制输入的不对称分布的细胞组成。 在这里，我们建议使用最先进的电生理和成像技术相结合，以确定这两个基本特征的方向选择性的发展背后的机制-电路的无效侧抑制和方向选择性神经节细胞马赛克的存在。特别是，我们将确定自发性视网膜活动是否在这些回路的形成中起关键作用。 公共卫生相关性：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的能力的基础电路。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，这种反射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回路的布线中扮演什么角色。发展对支配电路正常发育的组织原则的详细理解，可能使理解神经性出生缺陷的起源成为可能。在发育的早期，在视觉体验成为可能之前，电和化学活动在整个未成熟的视觉系统中自发地产生。越来越多的证据表明，这种早期活动对于调节视觉的电路的适当发展至关重要。这些发现使我们了解了为什么胎儿暴露于药物制剂会导致各种神经病理学。此外，深入了解神经活动的作用将为设计策略提供重要见解，这些策略允许神经系统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.