The overall goal of the proposed research is to learn- more about the roles of the parallel X, Y, and W pathways in visual system function and development. Two approaches will be taken during the proposed grant period. The first approach is to use monoclonal antibodies as molecular markers for studies of the visual pathways. During the current grant period, we have generated eight monoclonal antibodies that bind selectively to neurons in the ganglion cell layer (GCL) of the cat retina. During the proposed grant period, we will carry out studies to identify which classes of GCL neurons are labeled by each of the antibodies. This will be done by anatomical studies of the morphology and central projections of the labeled retinal neurons. In addition, we will determine whether the antibodies label neurons in the lateral geniculate nucleus (LGN) and striate cortex and identify the types of neurons that are labeled. If any of the eight antibodies binds to a specific morphological or physiological cell class in the retina, LGN, or striate cortex, we will use the antibodies as molecular markers for studies of the projections and development of cells that bear the target antigen. The second approach that will be taken during the proposed grant period is to use selective antibodies to eliminate specific pathways in the visual system. We will begin by determining whether any antibodies that bind to a specific cell class can be used alone, or conjugated to a cytotoxin, to damage target neurons. If any of the antibodies or conjugates can be used as selective toxins, we will start neurophysiological studies of the effects of removing the targeted cell class on visual system function. These experiments are related to health in that they will help elucidate the brain mechanisms of vision. In addition, a number of diseases (e.g., amblyopia, glaucoma, diabetic retinopathy, multiple sclerosis, and Alzheimer's disease) have symptoms that have been related to abnormalities in one of the parallel pathways, and the proposed experiments will help elucidate the mechanisms of the abnormalities.
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