The neurobiology of deprivation-induced amblyopia

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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.