DENDRITIC MORPH0LOGY AND THALAMIC INNERVATION IN PREFRONTAL SCHIZOPHRENIC CORTEX

许多证据表明，前额叶皮层与精神分裂症有关（综述见Shapiro，41）。最近Selemon等人，(42)描述了第9区III-V层神经元密度的增加，Benes等人，(5)描述了精神分裂症患者背外侧前额叶皮层10区神经元密度的类似增加。他们假设神经元密度的增加可能是由于树突结构的萎缩性变化。我们建议直接测试这一假设，通过分析细胞骨架和形态的树突在几个领域的前额叶皮层（第9，10和32区）的前瞻性特征队列的精神分裂症患者和年龄和性别匹配的控制。此外，三个皮质区中的两个，即第9区和第20区，接受来自内侧背核的丘脑传入，这些传入在精神分裂症患者中表现出体积和细胞数量的减少。丘脑输入的皮层已被证明是重要的，在帮助树突修剪在发展过程中。因此，皮层神经支配的变化可能导致树突结构的改变。从内侧背核到皮质的不同投射神经元群体含有钙结合蛋白或小清蛋白，钙结合蛋白。霍夫等人，(25)已经表明，皮质中的神经纤维染色与丘脑传入相关。因此，我们建议检查是否丘脑体积和细胞损失的变化将映射到皮层作为丘脑传入神经的变化。因此，我们建议检查是否在丘脑体积和细胞损失的变化将映射到皮层作为丘脑输入的变化。我们建议使用免疫组化染色的两个钙结合蛋白，钙结合蛋白和小清蛋白。为了获得数据，很少有研究评估锥体细胞中可能发生的形态学变化，以解释可能的萎缩性变化。 此外，很少有研究试图将精神分裂症中受影响的不同皮层和皮层下区域联系起来。该项目是首次尝试了解精神分裂症患者前额叶皮层树突形态的可能变化，并将丘脑中正在进行的工作与可能发生在相关皮质领域的变化联系起来。

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.