Mechanisms of retinotectal map development

视网膜顶盖图发育机制

• 批准号: 6596493
• 负责人: GEOFFREY J GOODHILL
• 金额: $ 11.64万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-01 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6596493
• 关键词: intercellular connection; mathematical model; model design /development; neuroanatomy; neuronal guidance; retina; superior colliculus; vision; visual pathways

DESCRIPTION (provided by applicant): Visual maps are crucial for visual function. Understanding the mechanisms by which visual maps develop and regenerate is therefore crucial for understanding how vision develops, and how vision could be restored after injury. Perhaps the most important model system for visual map development is the topographic projection from the retina to the tectum/superior colliculus. Although the mechanisms of map formation in this system have been studied experimentally for many decades, there is no unifying theoretical framework that can explain more than a small subset of this data. Without such a framework it is impossible to rigorously state what the mechanisms underlying map formation in the retinotectal system really are, and it is difficult to extrapolate beyond current data to predict how novel perturbations to the system will affect map development. Although several theoretical models of retinotectal map formation have been proposed previously, they have two serious limitations. Firstly, they generally address only refinements to map topography by activity-dependent Hebbian learning rules, and do not address how initial topography forms by activity independent processes. Secondly, they generally take no account of any of the data that has emerged since 1995 on the crucial role of ephrin/Eph gradients in retinotectal map formation. To overcome these problems, we propose to develop a comprehensive new model which (1) is based on axon guidance by molecular gradients rather than Hebbian learning rules, and (2) synthesizes recent data on ephrin/Eph gradients with older data regarding surgical manipulations to the system. The PI is in a unique position to be able to do this, since he combines a detailed knowledge of the extensive experimental data in this area with wide-ranging experience in the theoretical modeling of axon guidance and map formation in the visual system. The outcome of this project will be a computational framework that rigorously identifies the relative contributions of mechanisms such as chemotaxis and competition to the formation of retinotectal maps, makes testable predictions, and can guide future experimental work.

描述（由申请人提供）：视觉图对于视觉功能至关重要。 因此，了解视觉图发育和再生的机制对于理解视力如何发育以及视力如何在受伤后恢复至关重要。 也许视觉图开发最重要的模型系统是从视网膜到顶盖/上丘的地形投影。 尽管该系统中地图形成的机制已经通过实验研究了数十年，但没有统一的理论框架可以解释这些数据的一小部分。 如果没有这样的框架，就不可能严格说明视网膜顶盖系统中地图形成的机制到底是什么，并且很难根据当前数据进行推断来预测系统的新扰动将如何影响地图发展。 尽管之前已经提出了几种视网膜顶盖图形成的理论模型，但它们有两个严重的局限性。首先，它们通常仅解决通过依赖于活动的赫布学习规则来绘制地形图的细化，并且不解决初始地形如何通过活动独立过程形成的问题。其次，他们通常没有考虑自 1995 年以来出现的关于 ephrin/Eph 梯度在视网膜顶盖图形成中的关键作用的任何数据。为了克服这些问题，我们建议开发一种全面的新模型，该模型（1）基于分子梯度的轴突引导而不是赫布学习规则，（2）综合了肝配蛋白/Eph梯度的最新数据与有关系统手术操作的旧数据。 PI 处于能够做到这一点的独特位置，因为他结合了该领域大量实验数据的详细知识以及视觉系统中轴突引导和地图形成的理论建模的广泛经验。 该项目的成果将是一个计算框架，该框架严格识别趋化性和竞争等机制对视网膜顶盖图形成的相对贡献，做出可测试的预测，并可以指导未来的实验工作。