The mammalian primary visual cortex is probably better understood in its circuitry and neuronal response properties than is any other region in the vertebrate brain. This thorough knowledge of adult anatomy and physiology makes visual cortex an attractive model for studies of the establishment of specific neuronal connections during development. Development of the cortical response properties of ocular dominance and orientation selectivity have been widely studied, with results highlighting the importance of competition and patterned neuronal activity for the development of normal structure and function in the visual cortex. To date, however, little is known about the development of connections underlying the separate processing of lightness and darkness information carried from the retina to the brain in parallel channels of ON-center and OFF-center retinal ganglion cell axons. The proposed experiments will study the development of the ON- and OFF-center pathways in the ferret, an animal which has strict anatomical segregation of the two pathways in ON- and OFF-center leaflets in the lateral geniculate nucleus (LGN) and in patches of ON- and OFF-center afferent input to primary visual cortex. In order to determine the importance of the functionally distinct ON and OFF pathways during development, ferrets will be raised with the ON-center pathway silenced by intravitreal injections of the glutamate analog 2-amino-4-phosphonobutyric acid (APB). The effects of this ON-center activity blockade will then be assessed at the levels of the retina, LGN and cortex. Anatomical and electrophysiological studies of the retinal inner plexiform layer, the LGN and the cortex will determine whether the ON-center activity blockade has prevented the normal segregation of ON- and OFF-center information in the visual system. The effects of the APB treatment on cortical response properties and circuitry will then be assessed. Receptive field properties of individual cortical neurons will be studied using extracellular recording techniques, and the maps across cortex will be examined using optical imaging. Special attention will be paid to the orientation specificity of cortical neurons since orientation has been proposed to rely on separate ON and OFF-center pathways in several quantitative developmental models of cortex. The patterns of afferent input to the cortex will be determined electrophysiologically and intra-cortical connections will be examined using fluorescent tracers. The results of these studies will illuminate the role of the ON-center pathway in the development of the mammalian visual system, and will help determine how well developmental rules gleaned from studies of ocular dominance and orientation fit other visual modalities, which may in turn lead to a greater understanding of all developmental processes and abnormalities including those found clinically in humans.
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