Elements of the general plastic response of the brain, ranging from synaptic proliferation and structural modification to modifications of non-neural elements have been under study by a large number of neuroscience laboratories. A variety of changes in the structure Of individual synapses, as well as changes in the number and pattern of synapses, have been described in Paradigms ranging from electrically-induced long-term Potentiation in vitro to various types of adult learning. As a result, these changes have tended to be viewed individually as potential forms of efficacy or circuitry change, rather than as components of an overall pattern or set of patterns that define a coherent plastic process. This proposal seeks to understand neural plasticity in a more complete context. Both plasticity of synapse number--the formation and loss of synapses-and plasticity of synapse structure--the presumed modification of previously existing synapses--will be investigated in the occipital cortex of young and adult rats housed in complex or individual cage environments. The experimental plan combines use of Phaseolus vulgaris leucoagglutinin (PHA-L), wheat germ agglutinin-horseradish peroxidase (WGA-HRP), and l,l',dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Di-I) based analysis of afferent axons with current source density (CSD) analysis of responses evoked by activation of these afferents. Subjects will be rats in which these afferents have (or have not) been altered as a consequence of housing in a complex environment. Electron microscopic analysis of PHA-L labelled synapses will evaluate modifications in the structure of synapses in identified afferent systems to determine which forms of structural plasticity are dissociated from plasticity of synapse number, and hence are the most likely candidate substrates for synaptic efficacy change. Functional correlates of structural modifications will be assessed through laminar CSD analysis of responses evoked by activation of the particular afferent system under study. Parallel experiments will examine two additional key components of the general plastic process as exhibited in the EC-IC rat model: changes in the number and structure of astrocytes and changes in the structure of the capillary network. Thus the proposal seeks to develop an integrated understanding of the process of neural plasticity, as exhibited in the rat occipital cortex.
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