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、情感和动机等过程的贡献是必不可少的。它们定义了使用实验动物的基础科学功能研究和使用人类行为和功能成像方法的临床科学功能研究的竞争领域。神经系统疾病，如阿尔茨海默病和颞叶癫痫，以及精神疾病和发育疾病，如精神分裂症和自闭症，都以中脑皮层为目标。目的1将研究人脑穿孔通路的组织，利用阿尔茨海默病的内嗅神经原纤维缠结病变，使其变性终末对异常磷酸化的tau蛋白分子产生免疫反应。这种病变也在穿孔通路末端区诱导发芽，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，以及大脑对它的反应，并勾勒出对记忆至关重要的神经系统。目的2将研究微血管毛细血管对人脑穿孔通路起源细胞的供应。这将揭示，这些神经元是包裹在一个独特的毛细血管合，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将研究识别皮层输入到猴子穿孔通路起源神经元的性质，并利用路西法黄细胞内填充进行表型识别。共聚焦激光扫描显微镜将显示突触素标记的突触前末端连接已确定的穿孔通路神经元。所有的目的都是解决内嗅皮质模块化的一般主题，并利用各种方法和两种灵长类动物。这项研究将在一个长期致力于理解灵长类动物大脑结构和功能关系的实验室进行，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).