The neurobiology of deprivation-induced amblyopia

出生后早期的视觉经验指导神经连接的发展，以支持正常的视觉功能。在大脑发育的这个形成期，神经元及其连接可能会被改变感觉活动模式的眼部疾病所改变。例如，在生命早期剥夺一只眼睛的视力会导致结构改变，产生萎缩的神经元胞体，细小而曲折的树突，并减少轴突终末野。这些解剖学上的干扰被认为是导致弱视的视觉障碍，弱视与视觉体验中断有关。我的研究重点是了解感官输入在构成哺乳动物主要视觉通路的神经元发育中所起的作用。我们的目标是揭示由异常视觉体验带来的大体结构变化的亚细胞介体，这可能是视觉功能受损的基础。我们的研究表明，细胞骨架的破坏和神经元结构的改变之间存在因果联系，这引发了我们的信念，即细胞骨架的改变是神经元结构发生重大变化的必要先兆。这项建议的一个主要目的是了解感觉剥夺如何影响正常细胞结构的崩溃，并确定这可能如何导致弱视。我们将研究不同形式的视觉剥夺对神经元结构和组成细胞骨架的蛋白质的影响。在视觉缺乏的动物中，我们将通过一种方法来评估并行视觉处理流的完整性，该方法允许跨不同细胞类别同时检查细胞结构和蛋白质组成。这些研究有望在神经科学中一个长期存在的问题上开辟新的天地，即神经元结构如何因感觉输入中断而发生根本性变化，以及这种变化与随后的视力损害有何关系。了解视觉剥夺的基础有望为早期生活经验产生的知觉障碍的起源和恢复提供重要的洞察力。

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.