Cortical Dynamics and Neural/Behavioral Performance

皮质动力学和神经/行为表现

• 批准号: 10058278
• 负责人: David McCormick
• 金额: $ 73.75万
• 依托单位: UNIVERSITY OF OREGON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10058278
• 关键词: Action Potentials; Address; Animals; Arousal; Attention deficit hyperactivity disorder; Auditory; Behavior; Behavior monitoring; Behavioral; Brain; Brain Diseases; Caliber; Cerebral cortex; Detection; Disease; Funding; Goals; Image; Influentials; Investigation; Laboratories; Measures; Membrane Potentials; Mus; Nature; Neurons; Pathway interactions; Performance; Property; Pupil; Pyramidal Cells; Research Personnel; Schizophrenia; Sensory; Sorting - Cell Movement; Synapses; System; Techniques; Variant; Whole-Cell Recordings; autism spectrum disorder; awake; behavioral response; brain behavior; neuroregulation; operation; optogenetics; relating to nervous system; response; sensory stimulus; two-photon

What are the cellular and network cortical mechanisms of optimal neural and behavioral performance? Through what mechanisms do spontaneous and evoked changes in the waking state of the cortex influence sensory processing and behavior? The goal of my laboratory is to answer these broad and important questions at levels extending from cellular and synaptic properties, to local circuits, to thalamocortical networks, modulation, and behavior. Answering these questions are fundamental not only to understanding the normal operation of the brain, but also its operation in a variety of disorders, from schizophrenia, to ADHD, autism, and others. Our proposal is ambitious, but not unreasonable or unfocused. We have already made significant progress towards a broad outline of important pieces of the puzzle, and therefore are confident that we will make very significant progress towards a detailed clarification of these two fundamental questions during the funding period. More than a hundred years ago, two investigators, Yerkes and Dodson, noted that optimal performance on difficult detection tasks was related to arousal level in an “inverted-U” shaped fashion. Increases from low arousal to intermediate arousal would enhance performance on difficult tasks, while further increases in arousal from intermediate to high would decrease performance. This result suggests that there is an “optimal state” for both the brain and behavior. Surprisingly, until our recent study in behaving mice performing a difficult auditory detection task, the cortical activity or circuit representation of optimal state had not been investigated. Our investigation revealed that the optimal state for performance of a difficult auditory sensory detection task occurred at intermediate levels of arousal and was associated with the suppression of slow corticocortical and thalamocortical activity, a hyperpolarized and low variability of pyramidal cell membrane potential, and large amplitude and highly reliable evoked auditory cortical synaptic responses. In an indication of the broad nature of these effects, we observed that we could predict more than half of the variance in cortical neuronal membrane potential, action potential, and even behavioral performance simply by measuring the pupil diameter – an easily obtained measure of rapid (second to second) fluctuations in behavioral state. By explaining a large fraction of neuronal and behavioral variance, we have demonstrated that the brain is much more precise and reliable than previously thought. Here we propose to reveal the detailed cellular, modulatory, and network mechanisms that account for these prominent effects of state variation on neural and behavioral performance. Through a combination of state-of-the-art imaging, whole cell recording, optogenetic manipulation, and high quality behavioral monitoring, we will be able to detail the contribution of multiple neuronal and neuromodulatory pathways to the determination of optimal state for neural/behavioral responses.

最佳神经和行为性能的细胞和网络皮质机制是什么？ 通过哪些机制在皮质影响的唤醒状态中发挥了赞助和诱发的变化 感官处理和行为？我实验室的目的是回答这些广泛而重要的问题 在从细胞和突触特性延伸到本地电路，再到丘脑皮质网络的水平， 调制和行为。回答这些问题是基本的，不仅要了解正常 大脑的操作，以及其在各种疾病中的运作，从精神分裂症到多动症，自闭症和 其他的。我们的提议是雄心勃勃的，但不是不合理的或没有关注的。我们已经很重要 朝着重要的难题的广泛概述迈进，因此有信心我们将做出 在资金期间，详细阐明这两个基本问题的详细阐明了非常重大的进展 时期。 一百多年前，两名调查人员Yerkes和Dodson指出了最佳性能 在艰难的检测任务上，任务与“倒立”形式的唤醒水平有关。从低点增加 唤醒到中间的唤醒将提高艰巨的任务的性能，而唤醒进一步增加 从中间到高将降低性能。该结果表明有一个“最佳状态” 大脑和行为。令人惊讶的是，直到我们最近的行为表现出艰难的听觉的研究 尚未研究检测任务，最佳状态的皮质活动或电路表示。我们的 调查表明，执行困难的听觉感官检测任务的最佳状态 发生在唤醒的中间水平，与抑制缓慢的皮质皮质和 丘脑皮质活性，锥体细胞膜电位的超极化和低变异性，并且很大 放大器和高度可靠的诱发听觉皮质突触反应。表明广泛的本质 在这些影响中，我们观察到我们可以预测皮质神经元膜方差的一半以上 仅通过测量学生直径，潜力，行动潜力甚至行为表现 - 简单 在行为状态下，获得了快速（第二到第二）波动的测量。通过解释很大一部分 神经元和行为差异，我们已经证明大脑比 以前想到。在这里，我们建议揭示详细的细胞，调节和网络机制 解释了国家差异对神经和行为表现的显着影响。通过一个 最先进的成像，全细胞记录，光学遗传操作和高质量的结合 行为监测，我们将能够详细介绍多种神经元和神经调节的贡献 确定神经/行为反应最佳状态的途径。