Development of direction selectivity in retina

视网膜方向选择性的发展

基本信息

批准号：
8108211
负责人：
Marla Feller
金额：
$ 36.88万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-01 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8108211
关键词：
Ablation Accounting Address Affect Age Amacrine Cells Automobile Driving Cells Chemicals Congenital Abnormality Dendrites Development Exposure to Fetus Funding Future GABA Receptor Generations Goals Grant Image Imaging Techniques Inhibitory Synapse Interneurons Lead Left Light Mediating Modeling Morphology Motion Movement Nervous system structure Neurologic Play Positioning Attribute Process Proteins Published Comment Reflex action Research Retina Retinal Retinal Ganglion Cells Role Shunt Device Side Structure Synapses Testing Time Transgenic Mice Transgenic Organisms Trees Vision Visual Visual system structure Work design experience ganglion cell insight mouse model neural circuit neuronal cell body neuropathology object motion oculomotor preference receptive field relating to nervous system research study response vision development

项目摘要

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.

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的反应强烈，并且对朝相反或无效的图像移动，并且对于驱动我们在视觉场景中移动时稳定视网膜上稳定图像的眼部运动反射至关重要。方向选择性神经节细胞的首选方向沿着基本方向（向上，向下，左右和右）聚集，并且对每个基本方向敏感的方向选择性神经节细胞都被组织成镶嵌物，以便在空间中的每个点，每个运动方向都表示。在视网膜中产生方向选择性的主要模型是，在方向选择性神经节细胞的树突树的零树上，特定类别的中间神经元形成抑制性突触。指导在发育过程中抑制性输入不对称分布的细胞组成的镶嵌物的出现的机制尚不清楚。在这里，我们建议使用最先进的电生理学和成像技术的组合来确定这两个方向选择性的基本特征的发展的机制 - 源自无侧抑制的电路以及方向选择性神经节细胞的存在。特别是，我们将确定自发性视网膜活性在这些电路的形成中是否起关键作用。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在视觉场景中检测物体运动方向的能力的基础的电路。这种“方向选择性”对于正常的视觉驱动反射至关重要，在我们通过视觉场景移动时，在视网膜上稳定图像。我们的工作将决定视网膜在这些方向选择电路的接线中的角色神经活动。对控制电路正常发展的组织原理有详细的理解可能使了解神经出生缺陷的起源成为可能。在开发的早期，在可能的视觉体验可能是在整个未成熟的视觉系统中自发产生的电活动和化学活性。越来越多的证据表明，这种早期活动对于适当发展视力的电路的适当发展至关重要。这些发现为我们提供了有关为什么胎儿暴露于药理学剂会导致各种神经病理学的见解。此外，获得对神经活动作用的见解将为制定策略提供关键的见解，使神经系统能够重新连接正常的神经回路，以应对影响视力的发育异常。