CYTOMETRIC AND IMMUNOCYTOCHEMICAL CORRELATES IN SCHIZOPHRENIC PREFRONTAL CORTEX

这个项目的长期目标是解剖解剖 前额叶皮层的内在电路组织， 在正常人、猴子和选定的 精神分裂的大脑 重点继续放在 细胞结构、局部回路和单胺能神经支配 联想和选定的感觉皮层区域，参考 在这个实验室和其他实验室里对精神分裂症患者大脑的研究结果。 这个项目沿着沿着三条调查线被细分。 1)纳入不断 精神分裂症皮层神经病理改变的研究， 建议增加一个新的病例队列，并扩大细胞计数 研究包括区域8，人类额叶视野，和区域 45，布罗卡区;我们希望证实和扩大增加的证据， 在Brodmann第9区和第46区获得的细胞密度和神经元密度降低， 并确定蜂窝变化是否特定于关联区域 并在这些领域内，以特定的神经元群体; 2）研究 人类前额叶皮层的内在回路将解决 精神分裂症患者的细胞密度增加是由于丢失或重排 皮质内连接和/或树突状分支萎缩 使用荧光示踪剂，例如，dil和高尔基体， 分别 对识别出的抑制性中间神经元的输入也将是 在恒河猴和人类大脑皮层中进行免疫细胞化学检查， 在光学和电子显微镜水平上进行分析; 3）我们将继续 突触结构的超微结构特征 化学定义的传入对确定的皮质目标，引导 假设去甲肾上腺素、血清素和乙酰胆碱 在皮层覆盖层内有优先的终止模式， 就像我们证明的多巴胺能神经支配一样。 双标记 免疫细胞化学范例也将用于揭示解剖学 这些系统之间的相互作用在前额叶的基板 恒河猴的大脑皮层，最终进入人类大脑。 的 神经递质和受体特异性抗体的可用性， 识别受体合成神经元的mRNA探针，其中一些 在拟建中心的项目III中开发，将允许 我们获得一个全面的看法，前和突触后的元素， 特定的神经递质系统，从而获得更明确的 了解他们的精神活动。

The long range goal of this project is to anatomically dissect the intrinsic circuit organization of the prefrontal cortex at light and electron microscopic levels in normal humans, monkeys, and in selected instances, schizophrenic brains. Emphasis continues to be placed on the cytoarchitecture, local circuits, and monoaminergic innervation of associational and selected sensory cortical regions, with reference to findings obtained on schizophrenic brains in this and other laboratories. The project is subdivided along three lines of inquiry. 1) In ongoing investigations of neuropathological changes in schizophrenic cortex, we propose to add a new cohort of cases as well as expand cytometric investigation to include area 8, the human frontal eyefields, and area 45, Broca's area; we hope to confirm and extend evidence of increased cell density and decreased neuropil obtained in Brodmann's area 9 and 46, and determine whether cellular changes are specific to association areas and, within these areas, to specific neuronal populations; 2) Studies of intrinsic circuitry in human prefrontal cortex will address whether increased cell density in schizophrenics is due to loss or rearrangement of intracortical connections and/or atrophy of dendritic arborizations using fluorescent tracers, e.g., diI, and Golgi impregnations, respectively. Inputs to identified inhibitory interneurons will also be examined in rhesus monkeys and human cortex in immunocytochemical analyses at the light and electron microscopic level; 3) We will proceed with the ultrastructural characterization of the synaptic architecture of chemically defined afferents on identified cortical targets, guided by the hypothesis that norepinephrine, serotonin, and acetylcholine each have preferential patterns of termination within the cortical mantle just as we demonstrated for the dopaminergic innervation. Double labeling immunocytochemical paradigms will also be used to reveal anatomical substrates of the interaction among these systems in the prefrontal cortex of rhesus monkeys, and ultimately in the human brain. The availability of neurotransmitter - and receptor-specific antibodies and mRNA probes which recognize receptor-synthesizing neurons, some of which are being developed in Project III of this proposed Center, will allow us to gain a comprehensive view of pre-and postsynaptic elements of specific neurotransmitter systems and thereby to gain a more explicit understanding of their psychoactive efforts.