EARLY EXPERIENCE AND ADULT CORTICAL PLASTICITY

早期经历和成人皮质可塑性

• 批准号: 2891879
• 负责人: JAMES STACY MCCASLAND
• 金额: $ 20.17万
• 依托单位: UPSTATE MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-31 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2891879
• 关键词: NMDA receptors; animal developmental psychology; behavioral /social science research tag; brain metabolism; deoxyglucose; developmental neurobiology; dizocilpine; early experience; glucose metabolism; hamsters; immunocytochemistry; inhibitor /antagonist; neural plasticity; neural transmission; neurogenesis; neuropharmacology; psychological adaptation; psychopharmacology; sensory cortex; sensory deprivation; vibrissae

The study of local circuits in cerebral cortex has relied on physiological measures of the responses of single neurons to stimulation. The obvious missing ingredient in current approaches to cortical function is the ability to study the normal function of large groups of neurons working together. We have developed an experimental procedure which makes it possible, for the first time, to study the metabolic activity of every immunohistochemically labeled neuron in a neural system of interest. The procedure combines a high-resolution 2-deoxyglucose (2DG) technique, immunostaining for glutamate decarboxylase (GAD) and other antigens, and extensively automated data collection and analysis. These materials allow a direct assessment of the extent of excitation and inhibition in individual neurons. We propose to make extensive use of this double-labeling technology to study local circuitry in the whisker- related barrel field of rodent somatosensory cortex. We will quantitatively map and analyze the cellular patterns of cortical 2DG labeling seen in behaving hamsters and mice. We will compare cortices from normal, acutely whisker-trimmed, artificially stimulated, and chronically whisker-trimmed rodents with respect to the underlying distribution of GAD and other immunostains. We will generate complete high resolution functional maps of the stimulated and surrounding portions of the barrel field, enabling accurate comparison of the metabolic activities in antigenically defined compartments across the cortex. From the database represented by these maps, we will test a number of specific hypotheses about cortical function and information flow in the trigeminal system of the behaving animal. A detailed comparison of our previous 2DG data and predictions derived from single-unit physiology shows good agreement despite vast differences in the two methods. We will pursue this line of evidence by looking for parallels in 2DG/immunostained materials to functional groups of neurons that have been physiologically characterized by other workers. We will then examine by anatomical means the projection fields of excitatory and inhibitory populations of neurons, and correlate the results of these measures with the extent of excitation and inhibition in individual neurons with different combinations of stimulated whiskers. We will assess the specific contribution of cortical and subcortical circuitry by comparing the activation patterns in various stations of the trigeminal pathway with the patterns of whiskers remaining on the face. Finally, we will characterize the plasticity in barrel cortex by comparing the normal patterns of cortical labeling with those observed following prolonged deprivation (whisker trimming) or artificial whisker stimulation.

对大脑皮层局部回路的研究依赖于 单个神经元对刺激的反应的生理测量。 目前研究大脑皮层功能的方法中明显缺失的成分 是研究大群神经元正常功能的能力 一起工作 我们开发了一种实验程序， 使得我们有可能，第一次， 神经系统中每个免疫组织化学标记的神经元的 兴趣 该程序结合了高分辨率2-脱氧葡萄糖（2DG） 技术，谷氨酸脱羧酶（GAD）和其他免疫染色 抗原，以及广泛的自动化数据收集和分析。 这些 材料允许直接评估激励的程度， 抑制单个神经元。 我们建议广泛使用 这种双标记技术可以研究触须中的局部电路， 啮齿动物躯体感觉皮层的相关桶场。 我们将定量地绘制和分析大脑皮层的细胞模式， 在行为正常的仓鼠和小鼠中观察到2DG标记。 我们将比较 正常的、修剪过胡须的、人工刺激的皮质， 和长期胡须修剪的啮齿动物， GAD和其他免疫染色剂的分布。 我们将生成完整的 刺激和周围环境的高分辨率功能图 部分桶场，使准确的比较 代谢活动的抗原定义区室跨 皮层 从这些地图表示的数据库中，我们将测试一个 许多关于皮层功能和信息的具体假设 在行为动物的三叉神经系统中流动。 我们以前的2DG数据和预测的详细比较， 尽管存在巨大的差异， 在这两种方法中。 我们将通过寻找 2DG/免疫染色材料与神经元功能群的相似性 其他工蚁的生理特征。 我们将 然后通过解剖学手段检查兴奋性和 神经元的抑制群体，并将这些结果 用个体的兴奋和抑制程度来衡量 神经元与不同的刺激胡须组合。 我们将 评估皮质和皮质下回路的具体贡献 通过比较不同站点的激活模式， 三叉神经通路与胡须的图案保留在脸上。 最后，我们将通过以下方式描述桶状皮层的可塑性： 比较正常的皮质标记模式与观察到的 在长时间剥夺（胡须修剪）或人工胡须后 刺激.