Plasticity of the adult visual cortex plays an important role in normal processes of perceptual learning as well as in functional recovery following central nervous system lesions. We propose in particular that the normal integrative processes seen in visual cortex are recruited for adaptive changes following CNS lesions. To understand the mechanisms underlying adult cortical plasticity, as well as its perceptual consequences, we will work with an experimental model involving the reorganization of cortical topography following binocular retinal lesions. We have made a computational model that relates the normal properties of visual cortical neurons to the changes occurring after retinal lesions, and further relates these changes to perceptual fill-in. In the current study we propose to test the predictions of this model, and to quantify the nature of the functional changes in V1 that ensue following retinal lesions. Monitoring the functional reorganization will be done by electrophysiological recordings in awake behaving monkeys, allowing us to follow the process of reorganization over multiple time points and over large areas of cortex. These experiments are also intended to resolve controversies concerning the prevalence, extent and nature of the remapping of cortical topography in the lesion model. To address issues of mechanism, we will explore the involvement of different components of cortical circuitry in the reorganization. This will be done by in vivo 2-photon imaging of cells, dendrites and axons labeled by neuronal infection with genetically engineered AAV virus carrying genes encoding different fluorophores. We will investigate the relative contribution of long-range horizontal connections, feedback connections from higher order cortical areas, and interlaminar connections within V1, as well as changes in dendritic morphology. With these experiments we hope to learn about the central mechanisms of recovery following retinal degenerations, such as macular degeneration and other forms of CNS damage. Our approach is also designed to further our understanding of the perceptual consequences of the cortical changes induced by retinal damage. Beyond their value in the study of lesion dependent plasticity, these studies will be of relevance to understanding the mechanism of normal experience dependent changes in the visual pathway, such as those associated with perceptual learning. The proposed experiments will help reveal the mechanisms of functional recovery following lesions and degenerative diseases of the CNS, including adult macular degeneration. The studies will also be relevant to understanding the normal experience dependent changes associated with perceptual learning, since the same circuits are likely to be involved.
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