This application proposes neurophysiological studies to elucidate the mechanisms by which patterns of neural activity may guide or affect the development and plasticity of the mammalian visual cortex. Our previous research has shown that spontaneous neural activity in the visual system is require for the development of ocular dominance columns in the visual cortex, an event that begins in utero in higher primates. Our more recent experiments have demonstrated a similar requirement for neural activity for the development of eye-specific laminae in the lateral geniculate nucleus; this process is essentially complete before the time of birth even in our feline model. The findings suggest that abnormalities in the spontaneous patterns of neural activity in utero may be a hitherto unsuspected cause of birth defects. In addition, and understanding in detail of the mechanisms of plasticity in the developing visual system should provide a rational basis to therapy for ambloyopia, a clinical disorder affecting as many as 2% of all children.
The specific aim of this proposal is to explore in detail the synaptic plasticity in the developing visual cortex produced by pharmacologically inhibiting the postsynaptic cortical cells. Our recent work has demonstrated that infusion of the GABA-A agonist muscimol into kitten visual cortex causes plasticity in favor of the less-active input when one eye is deprived of vision. The implications of this unprecedented phenomenon will be explored by determining the necessary does of a variety of inhibitory Agents, be delineating the period of susceptibility to the effects of these agents on cortical plasticity, by making quantitative measurements of visual responses following such plasticity, by conducting longer-term physiological experiments and anatomical studies of transneuronally labelled ocular dominance columns, and by pharmacological studies of effects on various receptor types.
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