Our objective is to continue our ongoing analysis of genetic and epigenetic factors that determine development of the visual system in the rhesus monkey. The experiments are designed to elucidate cellular and molecular mechanisms involved in normal and pathological development of the primate visual system. The planned experiments are best organized into five broad Specific Aims: (1) Biochemical characterization of developing visual connections, focusing now on the emergence of transmitters, transmitter receptors, and cell class-specific molecules, and the regulation of their distribution; (2) Experimental modifications of development in the visual system following prenatal enucleation, or ablation of subcortical and cortical centers, and artificial premature delivery; (3) Transcortical transplantations of prelabeled dissociated neurons and/or radial cylinders of cortical tissue of the occipital lobe to other cortical regions and vice versa in pairs of age-matched fetuses; (4) Regulation of the number of neurons, axons and synapses during development of the primate visual system in normal and experimentally altered states; and (5) Correlation between development of monkey and human visual systems. This series of interrelated experiments requires a battery of the most advanced techniques including: immunocytochemistry at light and EM levels using antibodies to neuroactive substances and various cell class-specific antigens, 3H-thymidine and in vitro binding receptor autoradiography, antero- and retrograde axonal transport tracing methods, transmission electron microscopy including reconstruction of cells and organelles from serial sections in combination with Golgi impregnation, 2-deoxyglucose metabolic mapping of neuronal activity, and psychophysical testing of visual function. These studies also require the performance of complex prenatal neurosurgery and transcortical transplantations. Furthermore, experiments are purposefully designed to allow each animal to be used for multiple studies. All investigations are conducted on the rhesus monkey with the ultimate goal of extrapolating the results to our understanding of mechanisms of normal and pathological development in the human nervous system and the prevention of congenital visual defects and blindness.
Showing the most recent 10 out of 44 publications
