NEUROPHYSIOLOGICAL & MODELING STUDIES OF LOCUS COERULEUS

神经生理学

• 批准号: 2891176
• 负责人: Gary S. Aston-Jones
• 金额: $ 27.63万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-29 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2891176
• 关键词: Macaca mulatta; attention; behavior prediction; behavioral /social science research tag; brain electrical activity; carbachol; clonidine; computational neuroscience; cues; locus coeruleus; male; microinjections; neuropharmacology; performance; psychological models; psychomotor reaction time; sensory discrimination; space perception; stimulus /response; visual perception

DESCRIPTION (adapted from applicant's abstract): The locus coeruleus- norepinephrine(LC-NE) system has long been implicated in arousal and alertness. This implies a relatively non-specific role for LC in cognitive function. However, the investigators' recent recordings from LC in the behaving monkey suggest a revision of this view. They have found that LC neurons respond to task-relevant stimuli in a selective, stimulus-specific manner, and that these cells exhibit two modes of activity corresponding to levels of performance in a visual discrimination task. Based on these findings, the investigators hypothesize that the LC helps to regulate the balance between selective vs. flexible behavior. They now have developed a computational model of LC and its influence on performance in cognitive tasks, which delineates mechanisms for such a function. This model predicts that the mode of LC activity influences the state of cortical function to promote either selective responding to task relevant stimuli or responsivity to a broader range of environmental stimuli, each of which may have adaptive value for behavior. Other of the investigators' results indicate that electronic coupling may be an important factor regulating the mode of LC activity. This proposal seeks to test these hypotheses, specifically in the context of tasks that involve visual spatial attention. The following studies are proposed: (1) The investigators will integrate our model of LC function into a model they have already developed of performance in a spatially-cued reaction time SCRT) task. (2) The investigators will record from monkey LC neurons during performance of the SCRT task, and analyze the relationship between LC activity and task performance, to test predictions made by the computational model. (3) The investigators will make local microinjections of selective pharmacologic agents into the monkey LC to transiently manipulate activity of, and electrotonic coupling among, LC neurons. This will test the causal role of LC in task performance, as well as the specific hypothesis that coupling among LC neurons is one means of regulating the mode of LC activity and the corresponding pattern of behavioral performance. (4) They will record visually responsive neurons in parietal cortex while recording and manipulating LC activity, to test mechanistic hypotheses concerning LC-NE influences on cortical function and task performance. The proposed program of research integrates computational modeling, neurophysiology, and behavioral studies to understand the functions of the LC-NE system, its interaction with cortical systems, and its regulation of the balance between task- directed behavior vs. responsivity to unexpected environmental stimuli.

描述（改编自申请人的摘要）：蓝斑- 去甲肾上腺素（LC-NE）系统长期以来一直与唤醒和 警觉。这意味着 LC 在以下方面的作用相对非特定： 认知功能。然而，调查人员最近的录音 行为猴子中的 LC 建议对这一观点进行修正。他们有 发现 LC 神经元以选择性的方式对任务相关的刺激做出反应 刺激特异性方式，并且这些细胞表现出两种模式 与视觉表现水平相对应的活动 歧视任务。根据这些发现，研究人员 假设 LC 有助于调节选择性之间的平衡 与灵活的行为相比。他们现在开发了一个计算模型 LC 及其对认知任务表现的影响，它描述了 此类功能的机制。该模型预测 LC 模式 活动影响皮质功能的状态，以促进 对任务相关刺激的选择性反应或对某项任务的反应 更广泛的环境刺激，每种刺激都可能具有适应性 行为价值。其他研究人员的结果表明 电子耦合可能是调节模式的重要因素 LC 活性。该提案旨在检验这些假设，特别是 在涉及视觉空间注意力的任务中。这 建议进行以下研究： (1) 研究人员将整合我们的研究成果 LC 功能模型转换为他们已经开发的模型 空间提示反应时间 SCRT）任务中的表现。 (2) 的 研究人员将记录猴子 LC 神经元的表现 SCRT任务，并分析LC活动与任务之间的关系 性能，以测试计算模型做出的预测。 (3) 研究人员将选择性地进行局部显微注射 药物制剂进入猴 LC 进行瞬时操作 LC 神经元的活性和电紧张耦合。这将测试 LC 在任务绩效中的因果作用，以及具体的 假设 LC 神经元之间的耦合是调节 LC活动模式和相应的行为模式 表现。 (4) 他们将记录视觉反应神经元 顶叶皮层，同时记录和操纵 LC 活动，以测试 关于 LC-NE 对皮质功能影响的机制假设 和任务表现。 拟议的研究计划整合了 计算模型、神经生理学和行为研究 了解 LC-NE 系统的功能及其与 皮质系统及其对任务之间平衡的调节 定向行为与对意外环境刺激的反应。