DENDRITIC MORPH0LOGY AND THALAMIC INNERVATION IN PREFRONTAL SCHIZOPHRENIC CORTEX

许多证据表明精神分裂症与前额叶皮层有关（回顾见Shapiro， 41）。最近Selemon等人（42）描述了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前额叶皮层背外侧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变化。我们建议通过分析具有前瞻性特征的精神分裂症患者队列以及年龄和性别匹配的对照组的前额叶皮层几个区域（9、10和32区）的细胞骨架和树突形态来直接验证这一假设。此外，三个皮质区域中的两个，9区和20区，接收来自内侧背核的丘脑传入信号，在精神分裂症患者中显示出体积和细胞数量的减少。丘脑皮层的输入已被证明在发育过程中帮助树突修剪是重要的。因此，皮层神经支配的改变可能导致树突结构的改变。从内侧背核到皮层的不同项目神经元群含有钙结合蛋白或小白蛋白，钙结合蛋白。Hoff等人（25）表明，皮层的neuropil染色与丘脑传入事件相关。因此，我们建议研究丘脑体积和细胞损失的变化是否会随着丘脑传入事件的变化而映射到皮层。因此，我们建议研究丘脑体积和细胞损失的变化是否会随着丘脑输入的变化而映射到皮层。我们建议采用免疫组织化学方法对钙结合蛋白calbindin和parvalbumin进行染色。在数据方面，很少有研究对锥体细胞可能发生的形态变化进行评估，以解释可能的萎缩变化。此外，很少有研究试图将受精神分裂症影响的不同皮层和皮层下区域联系起来。该项目首次尝试了解精神分裂症患者前额叶皮层树突形态可能发生的变化，并将丘脑正在进行的工作与可能发生在相关皮层区域的变化联系起来。

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.