MESOCORTICAL ANATOMY AND PLASTICITY

21-25年的更新描述了旨在了解形成人类和非人类灵长类大脑边缘叶的中皮质的结构组织的实验。这样的实验对于确定中皮质区域对学习和记忆、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努力，以及使用行为和功能成像方法的人类临床科学功能努力的竞争环境。神经疾病，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，都以中皮质为目标。目的1利用阿尔茨海默病的内嗅神经纤维缠结损伤，使其变性末端对异常磷酸化的tau蛋白分子产生免疫反应，研究人脑穿孔通路的组织结构。这种损伤还诱导穿孔通路终端区发芽，用酶和细胞黏附分子染色可以检测到。因此，多种方法将揭示退化以及大脑对退化的反应，并勾勒出这一对记忆至关重要的神经系统。目的2研究人脑穿支通路来源细胞的微血管供应。它将揭示这些神经元被包裹在一个独特的毛细血管合胞体中，以支持它们的高代谢和兴奋活动。研究结果将为人体功能成像研究奠定基础。目的3将研究已识别的皮质输入到猴子穿支通路起源神经元的性质，并利用荧光黄的细胞内填充来进行表型鉴定。共聚焦激光扫描显微镜将显示突触素标记的突触前终末与已鉴定的穿通径路神经元相连。所有目标都针对内嗅皮层模块化这一总主题，并利用各种方法和两个灵长类物种。这项研究将在一个有着悠久历史的实验室进行，致力于了解灵长类大脑中的结构和功能关系，以及神经疾病中这些关系的破坏。这是一项交互式研究，利用了哈佛医学院(1969-1978)和爱荷华大学(1979-现在)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).