PHYSIOLOGCIAL AND STRUCTURAL STUDIES OF NEURONS

神经元的生理和结构研究

基本信息

批准号：
7613346
负责人：
Douglas L Rosene
金额：
$ 33.9万
依托单位：
BOSTON UNIVERSITY MEDICAL CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/7613346
关键词：
Action Potentials Address Adult Age Age-associated memory impairment Aging Animals Area Astrocytes Behavioral Biological Preservation Calcium-Activated Potassium Channel Cell Count Cells Cognitive Collaborations Contralateral Count Data Defect Dependence Diffusion Diffusion Magnetic Resonance Imaging Disruption Elderly Fire - disasters Frequencies Functional disorder Gene Expression Generations Genes Glutamate Receptor Glutamates Harvest Hippocampal Formation Impaired cognition Impairment In Vitro Individual Inflammation Kinetics Learning Localized Longevity Magnetic Resonance Imaging Measures Medial Membrane Memory impairment Messenger RNA Methods Microglia Molecular Monkeys Myelin N(delta)-acetylornithine, -isomer N-Methylaspartate N-dodecanoylglutamic acid, -isomer, sodium salt NMDA receptor A1 Nerve Degeneration Neuronal Dysfunction Neurons Numbers Parahippocampal Gyrus Parietal Pathway interactions Pattern Performance Perfusion Physiological Physiology Polymerase Chain Reaction Prefrontal Cortex Preparation Property Prosencephalon Publications Pyramidal Cells Range Rate Reporting Rest Sampling Score Short-Term Memory Signal Transduction Slice Structure of rostrum of corpus callosum Synapses System T7 RNA polymerase Techniques Technology Temporal Lobe Testing Visual Cortex Work age effect age group age related alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid alpha-difluoromethyl-DOPA, -isomer alpha-methylornithine dihydrochloride, -isomer amino 3 hydroxy 5 methylisoxazole 4 propionate base cDNA Arrays cognitive function cohort design entorhinal cortex frontal lobe immunocytochemistry in vivo memory recognition middle age neuroimaging neuron loss neurophysiology patch clamp postsynaptic receptor research study response synaptic function voltage voltage clamp white matter white matter change young adult

项目摘要

Behavioral studies of aging monkeys demonstrate significant impairments that are likely to reflect neuronal dysfunction in the prefrontal cortex and medial temporal lobe but appear to be due to subtle disruption of neuronal function. The mechanisms of this dysfunction will be investigated according to four aims in using physiological, molecular, neuroimaging and neuroanatomical methods. First we will use the in vitro slice preparation to identify alterations in neuronal physiology including mechanisms underlying age-related defects in action potential generation and synaptic function. Second, we will harvest single physiologically characterized neurons from these slices and,in collaboration with Project 2, will use an adapation of single cell PCR to assess the expression of related genes and gene array technology to explore the range of changes in gene expression. Third, since a recent publications has described neuron loss confined to area 8A, we will use design-based stereology to obtain estimates of the total number of neurons in three adjacent areas of the prefrontal cortex (areas 9, 46 and 8A) and five adjacent areas of the medial temporal lobe (areas 28, 35, TH, TL and TF).And we will adapt stereological sampling to search for regional areas of loss within each of these areas. Fourth, to assess age-related changes in corticocortical pathways of the prefrontal cortex using in vivo neurophysiological methods to measure the compound action potential, diffusion tensor MRI to assess white matter integrity, and immunocytochemistry to assess activated microglia and reactive astrocytes in the same white matter pathways compared with the rest of the forebrain. These studies will be conducted in young adult, middle aged and elderly monkeys that have been behaviorally characterized on tasks assessing frontal lobe and medial temporal lobe function. By examining these issues in monkeys that cover the full adult life span we will be able to determine which changes occur first and their relationship to age-related cognitive decline.

老化猴子的行为研究表明，可能反映神经元的重大损害前额叶皮层和内侧颞叶功能障碍，但似乎是由于微妙的破坏神经元功能。该功能障碍的机制将根据使用的四个目的进行研究生理，分子，神经影像学和神经解剖学方法。首先，我们将使用体外切片准备确定神经元生理的改变，包括与年龄有关的机制动作电位产生和突触功能中的缺陷。其次，我们将在生理上收获这些切片中的神经元表征，并与项目2合作，将使用单一的适应细胞PCR评估相关基因和基因阵列技术的表达，以探索基因表达的变化。第三，由于最近的出版物描述了局限于地区的神经元损失 8a，我们将使用基于设计的立体学来获取三个相邻神经元总数的估计值前额叶皮层区域（9、46和8A区域）和内侧颞叶的五个区域（区域28、35，TH，TL和TF）。在每个领域中。第四，评估与年龄相关的与年龄相关的皮质皮质途径变化前额叶皮质使用体内神经生理学方法来测量复合动作电位，扩散张量MRI评估白质完整性和免疫细胞化学以评估活化的小胶质细胞与前脑的其余部分相比，在相同的白质途径中的反应性星形胶质细胞。这些研究将在成年，中年和老年猴子进行行为上进行以评估额叶和内侧颞叶功能的任务进行表征。通过检查这些问题在涵盖成人生活范围的猴子中，我们将能够首先确定哪些变化以及它们与与年龄有关的认知下降的关系。