NEUROPHYSIOLOGICAL & MODELING STUDIES OF LOCUS COERULEUS

神经生理学

基本信息

批准号：
6186783
负责人：
Gary S. Aston-Jones
金额：
$ 28.04万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-09-29 至 2003-08-31
项目状态：
已结题

项目摘要

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）：coeruleus- 去甲肾上腺素（LC-NE）系统长期以来一直涉及唤醒和警觉。这意味着LC在认知功能。但是，调查人员最近记录了表演猴子中的LC建议对这种观点进行修订。他们有发现LC神经元在选择性中对与任务相关的刺激做出反应，刺激特异性的方式，这些细胞表现出两种模式与视觉效果水平相对应的活动歧视任务。根据这些发现，调查人员假设LC有助于调节选择性之间的平衡与灵活的行为。他们现在已经开发了一个计算模型 LC及其对认知任务中表现的影响，该任务描述了这种功能的机制。该模型预测LC的模式活动会影响皮质功能的状态以促进两者选择性响应与任务相关的刺激或对更广泛的环境刺激可能具有自适应行为的价值。其他调查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。该建议旨在检验这些假设，特别是在涉及视觉空间关注的任务中。这提出了以下研究：（1）研究人员将整合我们 LC功能的模型成像他们已经开发的模型在空间反应时间SCRT）任务中的性能。（2）调查人员将在表演期间从猴子LC神经元记录 SCRT任务，并分析LC活动与任务之间的关系性能，测试计算模型做出的预测。（3）调查人员将进行当地的选择性。进入猴子LC的药理学剂进行瞬时操纵 LC神经元之间的活性和电耦合。这将测试 LC在任务绩效中的因果作用以及特定假设LC神经元之间的耦合是调节 LC活动的模式和相应的行为模式表现。（4）他们将记录视觉响应的神经元录制和操纵LC活动时的顶叶皮层，进行测试关于LC-NE对皮质功能的影响的机械假设和任务性能。拟议的研究计划集成了计算建模，神经生理学和行为研究了解LC-NE系统的功能，与皮质系统及其对任务之间平衡的调节 - 指示行为与对意外环境刺激的反应性。