Neuronal basis of sensory processing dysfunction in schizophrenia

精神分裂症是一种主要的精神障碍，影响大约1%的人口 全世界。认知功能障碍是这种疾病的一个核心特征，反映了广泛的皮质 以及皮质下神经元功能障碍。整个中心的目标是研究机制 精神分裂症潜在的感觉加工障碍，特别强调 谷氨酸/NMDA相关机制。精神分裂症患者的皮质加工障碍 一般与GABA能神经元内钙结合蛋白表达的改变有关 中间神经元，可能反映了谷氨酸能初级衰竭引起的二次下调 驾驶。本项目将检测细胞密度和GABA受体基因表达谱 精神分裂症患者初级视皮层中间神经元的激光捕获显微解剖研究 随着NKI/NYUSoM项目负责人开发的基因阵列表达技术，Dr。 Ginsberg，并将根据先前对海马星状细胞的基因阵列研究建立 精神分裂症患者表现为NMDA受体相关表达减少。该项目的联合负责人。Dr。 斯迈利是一位组织专家，他正在进行钙结合蛋白/GABA的研究 作为N1MH资助项目的一部分，听觉皮质中的中间神经元密度。降低的小白蛋白 在精神分裂症患者的前额叶皮质有广泛的表达，但感觉 人们对地区的研究仅限于有限的程度。对于这项研究的NKI部分， 将对死后的视皮层进行定量形态计量分析 精神分裂症和对照受试者。免疫细胞化学将用于鉴定GABA 中间神经元细胞类型，包括白蛋白、钙结合蛋白和钙视黄素细胞类型。的相对密度 然后对精神分裂症患者和对照组之间的GABA中间神经元进行比较。最后， 利用激光捕获显微切割，精选的钙结合蛋白和小蛋白神经元群体将被 由金斯伯格博士获取并处理以进行基因阵列分析。基因芯片分析将分析 钙结合蛋白、谷氨酸相关结构和其他更一般的表达水平 基因家族。

Schizophrenia is a major mental disorder that affects approximately 1% of the population worldwide. Cognitive dysfunction is a core feature of the disorder, reflecting widespread cortical and subcortical neuronal dysfunction. The goal of the overall Center is to investigate mechanisms underlying sensory processing disturbances in schizophrenia, with particular emphasis on glutamatergic/NMDA-related mechanisms. Cortical processing disturbances in schizophrenia in general have been linked to altered expression of calcium binding proteins within GABA-ergic interneurons, possibly reflecting secondary down regulation due to primary failure in glutamatergic drive. This Project will examine cell density and gene expression profiles of GABA-ergic interneurons in primary visual cortex in schizophrenia, using laser capture microdissection coupled with gene array expression techniques developed at NKI/NYUSoM by the Project Leader, Dr. Ginsberg, and will build as well from a prior gene array study of hippocampal stellate cells in schizophrenia showing reduced NMDA receptor-related expression. The project co-leader. Dr. Smiley, is an expert histologist who is pursuing ongoing studies of calcium binding protein/GABA interneuron density in auditory cortex as part of an NlMH-funded project. Decreased parvalbumin expression has been extensively documented in prefrontal cortex in schizophrenia, but sensory regions have been studied to only a limited degree. For the NKI component of the study, quantitative morphometric analyses will be performed on postmortem visual cortex from schizophrenia and control subjects. Immunocytochemistry will be used to identify GABA interneuron cell types, including pavalbumin, calbindin and calretinin cell types. Relative density of GABA interneurons will then be compared between schizophrenia and control groups. Finally, using laser capture microdissection, select populations of calbindin and parvalbumin neurons will be obtained and processed for gene array analysis by Dr. Ginsberg. Gene array analysis will analyze expression level of calcium binding proteins, glutamate-related constructs and other more general gene families.