This proposal represents the initial phase of a long-term project directed at the elucidation of cellular and anatomic features of neuronal organization that are specific to human language areas. This research effort will address three major issues: 1) What features of neuronal organization distinguish human cortical language areas from homologous areas in the opposite hemisphere? 2) When do divergent features of neuronal organization occur in the development of these homologous cortical areas? 3) Are there language and/or cognitive disorders that result from a failure of these homologous cortical areas to develop divergent features of neuronal organization? These studies will focus on temporal and parietal lobe regions that have been most clearly implicated in language processing, and that have been shown to exhibit hemispheric morphological asymmetries. As there is a lack of certainty as to the level of resolution necessary to detect differences in the neuronal organization of these homologous cortical areas, our initial studies will determine; 1) whether homologous cortical areas differ in their neuronal profiles, that is in their representation of neurons from different subclasses, and 2) whether during their development these homologous cortical areas differ in their selection and maturation of neurons from distinct neuronal subclasses. To assess these possibilities, we will conduct detailed quantitative analyses of three major chemically identified neuronal subpopulations in immunohistochemical preparations of adult and developmental human postmortem brains. The neuronal subpopulations to be studied include; 1) the subset of cortical pyramidal neurons that are immunoreactive to a monoclonal antibody that recognizes nonphosphorylated neurofilament proteins, 2) the subset of cortical interneurons that are immunoreactive to a monoclonal antibody recognizing parvalbumin, and 3) the subset of nonpyramidal and pyramidal neurons immunoreactive to a monoclonal antibody recognizing calbindin. Parvalbumin and calbindin are calcium binding proteins. In addition to these studies, we will further develop the techniques of intracellular filling in fixed tissue for their application in subsequent studies of these areas and for subsequent neuropathological studies. Although language and other learning developmental disorders have high incidences, little is known about their neuropathology. It is likely that an understanding of the neuropathological basis of these disorders will require detailed knowledge about the neuronal organization and maturation of cortical areas critical to language processing.
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