Visual Cortex Reorganization in Animal Model of Retinal Degeneration

The role of the dynamic nature of the brain is critical in the success of treatments aimed at restoring visions at the retinal level, such as bioelectronic implants and stem-cell therapy. Development of such approaches aims at treating the major blinding diseases such as retinitis pigmentosa (RP) caused by degeneration of photoreceptors, resulting in loss of visual inputs and remodeling of central nervous system circuitry. A recent study from China has reported that the prevalence of RP is about 1 in 1000 for a total of 1.3 million affected individuals throughout the country. The success of these treatments highly relies on the functionality of the surviving neurons along the entire visual pathway. Hence, not only the retina but the visual cortex also plays an important role to allow patients suffering from retinal disease to perceive the fine details of a visual scene. However, changes in sensory input can, over a period of time, alter receptive field and cortical topography.Cortical reorganization as a result of macular degeneration that causes a loss in central vision is studied in human adult visual cortex. Little is known about the remapping of cortex due to RP that causes a loss of peripheral vision. Currently, there is only one study (Gias et.al. 2011) reporting the degeneration of cortical function in animal model with retinal degeneration. The strength and size of the receptive fields of visual cortical neurons and alteration of retinotopic map during the course of retinal degeneration remain unknown.We propose a novel study the cortical reorganization after retinal degeneration by recording visual driven and spontaneous activity in the visual cortex of an animal model with rhodopsin mutation resembling the RP in humans (S334ter). In the first part of the study, we will determine the progress of cortical functional degeneration in S334ter rats after the loss of photoreceptors. Cortical responses for each recorded cell will be measured with electrophysiological recording. In the second part of the study, we will investigate the retinotpic activation in S334ter rat’s visual cortex. This study will provide information about the condition of the visual cortex after prolonged visual loss. This study will also unveil the functional connection between the inner retinal layers and the visual cortex in response to inner retinal stimulation. Physiological measurements in animal models should be helpful in guiding the development of retinal therapies and determine if degeneration or changes in visual cortex will limit the usefulness of retinal therapies.