MESOCORTICAL ANATOMY AND PLASTICITY

21-25年的更新描述了旨在理解形成人类和非人类灵长类大脑边缘叶的中皮层结构组织的实验。 这些实验对于确定中皮层区域对学习和记忆、情绪和动机等过程的贡献至关重要。 它们定义了使用实验动物的基础科学功能工作和使用人类行为和功能成像方法的临床科学功能工作的竞争环境。神经系统疾病，如阿尔茨海默病和颞叶癫痫，靶向中皮质，精神和发育疾病，如精神分裂症和自闭症。 目的1利用阿尔茨海默病的内嗅神经元缠结病变，研究人脑中的穿通通路的组织，该病变使其变性终末对异常磷酸化的tau蛋白分子呈免疫反应性。 这种病变还诱导在穿孔通路末端区的发芽，这可以用酶和细胞粘附分子染色检测到。 因此，多种方法将揭示退化和大脑对其的反应，并概述这种对记忆至关重要的神经系统。 目的2研究人脑穿通通路起源细胞的微血管供应。 它将揭示，这些神经元是陷入一个独特的毛细血管合胞体，以支持他们的高代谢和兴奋活动。 结果将为人类功能成像研究奠定基础。 目的3将研究猴子中识别的皮层输入到穿孔通路起源神经元的性质，并利用荧光黄细胞内填充进行表型鉴定。 共聚焦激光扫描显微镜下可显示突触素标记的突触前终末上连接识别的穿通通路神经元。所有的目标解决一般主题的内嗅皮质模块化，并借鉴了各种方法和两个灵长类动物物种。 这项研究将在一个有着悠久历史的实验室中进行，该实验室致力于了解灵长类动物大脑中的结构和功能关系，以及这些关系在神经系统疾病中的破坏。 这是一项互动研究，利用了哈佛医学院（1969-1978）和爱荷华州大学（1979-至今）31年来收集的大量数据。

This renewal for years 21-25 describes experiments aimed at understanding the structural organization of the mesocortices that form the limbic lobe of the human and non-human primate brain. Such experiments are essential for ascertaining the contributions of mesocortical areas to processes like learning and memory, emotion and motivation. They define the playing field, for both basic science functional efforts using experimental animals, and clinical science functional efforts using behavioral and functional imaging methods in humans. Neurological diseases, such as Alzheimer's disease and temporal lobe epilepsy target the mesocortices as do psychiatric and developmental diseases such as schizophrenia and autism. Aim 1 will investigate the organization of theperforant pathway in the human brain capitalizing on the entorhinal neurofibrillary tangle lesion of Alzheimer's disease which renders its degenerating terminals immunoreactive for the abnormally phosphorylated tau protein molecule. This lesion also induces sprouting in the perforant pathway terminal zone which is detectable with enzyme and cell adhesion molecule staining. Thus, multiple methods will reveal both degeneration, and the brains response to it, and outline this neural system critical for memory. Aim 2 will investigate the microvascular capillary supply to the cells of origin for the perforant pathway of the human brain. It will reveal that these neurons are enmeshed in a unique capillary syncitium to support their high metabolic and excitatory activity. Results will lay the groundwork for functional imaging investigations in the human. Aim 3 will investigate the nature of identified cortical input to the neurons of origin of the perforant pathway in the monkey and capitalize on Lucifer yellow intracellular filling for phenotype identity. Confocal laser scanning microscopy will reveal synaptophysin marked presynaptic terminals on connection identified perforant pathway neurons. All aims address the general theme of entorhinal cortical modularity and draw on a variety of methods and two primate species. This research will be conducted in a laboratory with a long history devoted to understanding structural and functional relationships in the primate brain, and the disruption of these relationships in neurological disease. It is interactive research that draws on a large body of data gathered over 31 years at Harvard Medical School (1969-1978) and The University of Iowa (1979-present).