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Mechanisms of retinotectal map development

视网膜顶盖图发育机制

基本信息

批准号：
6706971
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
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-03-01 至 2005-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6706971
关键词：
ephrins intercellular connection mathematical model model design /development neuroanatomy neuronal guidance retina superior colliculus vision visual pathways

项目摘要

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）：视觉地图对视觉功能至关重要。因此，了解视觉地图发展和再生的机制对于理解视觉如何发展以及受伤后视觉如何恢复至关重要。也许视觉地图发展的最重要的模型系统是从视网膜到顶盖/上级丘的地形投影。虽然在这个系统中地图形成的机制已经被实验研究了几十年，但没有统一的理论框架可以解释这个数据的一小部分。如果没有这样一个框架，就不可能严格地说明视网膜顶盖系统中地图形成的机制是什么，也很难在现有数据之外进行推断，以预测系统的新扰动将如何影响地图的发展。虽然先前已经提出了几种视网膜顶盖地图形成的理论模型，但它们有两个严重的局限性。首先，他们通常只解决的活动依赖的赫布学习规则，并没有解决初始地形的活动无关的过程中形成的地图地形的改进。其次，他们一般不考虑任何的数据，自1995年以来出现的关键作用的ephrin/Eph梯度在retinotectal地图的形成。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）基于分子梯度而不是Hebbian学习规则的轴突指导，以及（2）将最近关于ephrin/Eph梯度的数据与关于系统手术操作的旧数据相结合。PI处于一个独特的位置，能够做到这一点，因为他结合了在这一领域的广泛的实验数据的详细知识，在视觉系统中的轴突指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，严格确定的相对贡献的机制，如趋化性和竞争的视网膜顶盖地图的形成，使可测试的预测，并可以指导未来的实验工作。