Retinotopic representation of visual space is a general feature of mammalian visual cortex. Experiments in this proposal will study whether the retinotopic map is required for the physiological processing of sensory information. Specifically, the proposed work will study the consequences that genetically disrupted retinotopic maps have for receptive field properties, cortical circuits and visual behaviors. Several lines of mutant mice that display mapping errors in their visual cortex will be used, including the mice deficient in the molecular guidance cues ephrin-As, the mice that have disrupted patterns of spontaneous activity in the developing retina, and the mice in which these two disruptive interventions are combined. In addition, retinotopic maps will also be disrupted in wild type mice by misexpressing ephrin-As in the developing visual cortex. Using these mice, the investigators will first determine whether cortical receptive fields are abnormal when retinotopic maps are disrupted. Single-unit recordings will be performed to measure the size, orientation selectivity and spatial tuning of individual cortical neurons. By comparing the receptive field properties of mice that have different degrees of mapping errors, the contribution of topographic maps in shaping receptive fields in the visual cortex will be determined. Second, intracellular whole cell recording will be performed in the intact brain to study the pattern of intracortical synaptic inhibition in the absence of a precise retinotopic map. Finally, using a swimming test of visual discrimination and a test of optomotor response, the investigators will determine whether disruption of retinotopic maps affects visual behaviors. Together, these studies will elucidate the role of retinotopic maps in visual processing and will also help define how precise patterns of synaptic connections contribute to the normal behavioral output of the nervous system in general. Importantly, these experiments will reveal how mis-wired visual systems function at cellular, circuit and behavioral levels. Such knowledge will be useful for the understanding and treatment of disorders resulting from brain injury and from aberrant neuronal connections.
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