Much evidence implicates the prefrontal cortex in schizophrenia (for review see Shapiro, 41). Recently Selemon et al., (42) described an increase in neuronal density in layers III-V in area 9 and Benes et al., (5) described a similar increase in neuronal density in area 10 of the dorsolateral prefrontal cortex of schizophrenics. They hypothesized that the increase in neuronal density may be due to atrophic changes in dendritic architecture. We propose to directly test this hypothesis by analyzing both the cytoskeleton and morphology of the dendrites in several areas of prefrontal cortex (areas 9, 10, and 32) of a prospectively characterized cohort of schizophrenics and age and gender matched controls. In addition, two of the three cortical areas, areas 9 and 20, receive thalamic afferents from the medial dorsal nucleus that show decreases in both volume and cell number in schizophrenia. Thalamic input n the cortex has been shown to be important in aiding in dendritic pruning during development. Therefore, changes in innervation of the cortex may lead to alterations in dendritic architecture. Populations of the different project neurons from the medial dorsal nucleus to the cortex contain calbindin or parvalbumin, calcium binding proteins. Hoff et al., (25) has shown that the neuropil staining in cortex correlates with thalamic afferents. We therefore, propose to examine whether changes in thalamic volume and cell loss will map onto the cortex as changes in thalamic afferents. We therefore propose to examine whether changes in thalamic volume and cell loss will map onto the cortex as changes in thalamic input. We propose to use immunohistochemistry to stain for two calcium binding proteins, calbindin and parvalbumin. To data very little research has been done to assess morphological changes that could be occurring in the pyramidal cells to account for the possible atrophic changes. In addition, very little research has been performed to try to link different cortical and subcortical areas that are affected in schizophrenia. The proposed project is a first attempt to understand possible alterations in dendritic morphology in prefrontal cortex of schizophrenics and to link ongoing work in the thalamus with alterations that may be occurring in related cortical fields.
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