The neurobiology of deprivation-induced amblyopia

出生后早期的视觉经验指导支持正常视觉功能的神经连接的发展。在大脑发育的形成期，神经元及其连接可以通过改变感觉活动模式的眼部疾病进行修改。例如，在生命早期，一只眼睛的视力下降导致结构改变，产生萎缩的神经元胞体、薄而曲折的树突和减少的轴突终末场。这些解剖扰动被认为有助于视觉障碍，弱视，这是与破坏视觉体验。我的研究计划是专注于了解的作用，感觉输入在神经元的发展中发挥组成哺乳动物的主要视觉通路。我们的目的是揭示亚细胞介质的总体结构变化所带来的异常视觉体验，这可能是视觉功能障碍的基础。我们的研究表明，细胞骨架破坏和神经元结构的改变之间存在因果关系，这使我们相信细胞骨架的改变是神经元结构发生重大变化的必要前兆。这项建议的主要目的是了解感觉剥夺如何影响正常细胞结构的崩溃，并确定这可能导致弱视。我们将研究不同形式的视觉剥夺对神经元结构和构成细胞骨架的蛋白质的影响。在视觉剥夺的动物，我们将评估平行视觉处理流的完整性的方法，允许同时检查不同细胞类别的细胞结构和蛋白质组成。这些研究有望为神经科学中一个长期存在的问题开辟新的天地，即神经元结构如何被中断的感觉输入从根本上改变，以及这种变化如何与随后的视力障碍有关。了解视觉剥夺的基质，预计将提供重要的洞察起源和恢复知觉障碍，来自早期的生活经验。

Visual experience early in postnatal life instructs development of neural connections that support normal visual function. During this formative period in brain development, neurons and their connections can be modified by ocular disorders that alter sensory activity patterns. Deprivation of vision in one eye early in life, for instance, results in structural modifications that produce atrophied neuron somata, thin and tortuous dendrites, and reduced axon terminal fields. These anatomical perturbations are thought to contribute to a visual impairment, amblyopia, that is associated with disrupted visual experience. My research program is focused on understanding the role that sensory input plays in the development of neurons composing the mammalian primary visual pathway. We aim to bring to light the subcellular mediators of gross structural changes brought about by abnormal visual experience, and that may underlie impairments to visual function. Our research has suggested a causal link between cytoskeleton breakdown and modification of neuron structure, which has sparked our belief that modification of the cytoskeleton is a requisite precursor to gross changes in neuron structure. A principal aim of this proposal is to understand how sensory deprivation effects collapse of normal cell structure, and to determine how this might contribute to amblyopia. We will investigate the impact of different forms of visual deprivation on neuron structure and on proteins that compose the cytoskeleton. In visually deprived animals we will assess the integrity of parallel visual processing streams by a method that permits simultaneous examination of cytostructure and protein composition across different cell classes. These investigations are expected to break new ground on a long-standing problem in neuroscience, namely, how neuron structure is radically altered by disrupted sensory input, and how this change relates to subsequent vision impairment. Understanding the substrates of vision deprivation are expected to provide important insight into the origin of and recovery from perceptual impairments that derive from early life experience.