The mammalian primary visual cortex is probably better understood in its anatomy and physiology than is any other region in the vertebrate brain. Thorough knowledge in the adult makes the visual system an attractive model for studies of the establishment of specific neuronal connections during development. Development of cortical 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. The proposed experiments will study development of the visual pathways in the ferret, an animal that is born at a relatively early stage in development. In order to determine the importance of normal patterns of neuronal activity in the visual pathways during development, ferrets will be raised with either all activity or just ON-center activity in the retina silenced by intravitreal injections of the glutamate analog 2-amino-4-phosphonobutyric acid (APB) at different dosages and ages. Effects of these activity blockades will then be assessed in the lateral geniculate nucleus (LGN) and primary visual cortex. Anatomical studies of the LGN in animals raised with total retinal activity blockade have shown that activity is necessary not only to create eye-specific segregation in the LGN, but also to maintain it; in the absence of activity, retinal ganglion afferent arbors from the two eyes desegregate. The desegregated axons from both eyes in these animals project to the part of the LGN normally occupied only by axons from the contralateral eye. The proposed new studies will examine the physiological properties of LGN neurons in the animals with this novel pattern of retino-geniculate connectivity. Optical imaging and electrophysiological studies of ferrets raised with an ON-center activity blockade have shown that ON-center activity is necessary for the normal development of cortical cell orientation selectivity. Proposed experiments will study other receptive field properties of individual cortical neurons in animals raised with an ON-center blockade. The results of these studies will further illuminate the role that patterned activity plays in the development of the mammalian visual system, which may lead to a greater understanding of all developmental processes and abnormalities, including those found in humans.
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