The primary visual cortex is a model system for understanding the integration and processing of information at a cortical level. The cellular basis of this processing network consists of an elaborate network of intrinsic connections within and between the six cortical layers. In the first few months of life, the complexity of this circuitry increases tremendously, paralleling the emergence of distinct visual response properties in each of the layers. The primary goals of the proposed research are to understand the sequence of events underlying the development of these connections and the emergence of receptive field properties in the cat visual cortex, and to assess the extent to which these connections can be modified by visual experience. This work will utilize anterograde staining with PHA-L to visualized the differentiation of individual geniculo-cortical axons in order to determine if geniculate afferents originating from different laminae develop sequentially or in parallel. Intracellular injections of individual neurons in brain slices will then be used to assess the differentiation of dendrites of layer 4 spiny stellate cells, to determine whether the appearance of complex receptive properties in layer 3 is related to the emergence of connections between layers 4 and 2 3. The development of vertical and horizontal connections of layer 2 3 pyramidal cells will be studied to determine how the laminar specificity of vertical connections emerges, and when the system of clustered horizontal connections within layer 2/3 differentiates. This will be accomplished by identifying a particular class of layer 2/3 cells-those projecting to area 18- by combining a fluorescent retrograde tracer with intracellular dye injections in slices. The possible contribution of the layer 6 to 4 connection in generating end-inhibition will be evaluated by examining when this connection develops relative to the known physiological emergence of end-inhibition. Metabolic labelling with 2-deoxyglucose will be used to examine the overall pattern of orientation column development relative to afferent input and intrinsic circuit development. Finally, the question of whether intrinsic circuits can be altered by visual experience will be examined, by studying the effects of monocular deprivation and induced strabismus on the patterns of intrinsic circuits. These studies will use a combination of anterogradely transported and intracellularly injected fluorescent dyes to visualize the relationship between ocular dominance columns and intrinsic circuits. While previous work has emphasized the changes in afferent distribution resulting from deprivation or misalignment of the eyes, the experiments proposed here will provide the first glimpse of the involvement of intrinsic cortical circuits in these conditions, which cause profound visual dysfunction in humans, and which affect a significant number of young children. These investigations may bring to light previously unobservable consequences of these alterations in visual input, and suggest new therapies for treating or preventing cortical deficits.
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