Cortical Dynamics and Neural/Behavioral Performance

皮质动力学和神经/行为表现

• 批准号: 10530597
• 负责人: David McCormick
• 金额: $ 81.13万
• 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/10530597
• 关键词: Action Potentials; Animals; Arousal; Attention deficit hyperactivity disorder; Auditory; Auditory area; Behavior; Behavior monitoring; Behavioral; Brain; Brain Diseases; Cerebral cortex; Detection; Diameter; Disease; Funding; Goals; Image; Influentials; Investigation; Laboratories; Measures; Membrane Potentials; Mus; Nature; Neurons; Pathway interactions; Performance; Property; Pupil; Pyramidal Cells; Research Personnel; Schizophrenia; Sensory; Shapes; Sorting; Synapses; System; Techniques; Variant; Whole-Cell Recordings; autism spectrum disorder; awake; behavioral response; neural; neuroregulation; operation; optogenetics; response; sensory cortex; 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.

最佳神经和行为表现的细胞和网络皮质机制是什么？ 皮质清醒状态的自发变化和诱发变化通过什么机制影响 感觉处理和行为？我实验室的目标是回答这些广泛而重要的问题 从细胞和突触特性延伸到局部电路，再到丘脑皮质网络， 调制和行为。回答这些问题不仅对于理解正常情况至关重要 大脑的运作，以及它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。我们的建议雄心勃勃，但并非不合理或没有重点。我们已经取得了重大成果 在解决这个难题的重要部分的大纲方面取得了进展，因此我们有信心 在资助期间详细澄清这两个基本问题方面取得了非常重大的进展 时期。 一百多年前，两位研究人员 Yerkes 和 Dodson 指出，最佳性能 困难的检测任务与唤醒水平呈“倒U”形相关。从低位开始增加 唤醒到中等唤醒将提高困难任务的表现，同时进一步增加唤醒 从中级到高级会降低性能。这一结果表明，存在一个“最佳状态” 大脑和行为。令人惊讶的是，直到我们最近对表现出困难听觉的行为小鼠进行的研究 检测任务中，最佳状态的皮层活动或电路表示尚未被研究。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 发生在中等觉醒水平，并与慢皮质皮质和慢皮质皮质的抑制有关。 丘脑皮质活动，锥体细胞膜电位的超极化和低变异性，以及大 幅度和高度可靠的诱发听觉皮层突触反应。表明了广泛的性质 在这些影响中，我们观察到我们可以预测皮质神经元膜一半以上的方差 只需测量瞳孔直径即可轻松测量电位、动作电位，甚至行为表现 获得行为状态快速（秒到秒）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 之前以为。在这里，我们建议揭示详细的细胞、调节和网络机制 解释状态变化对神经和行为表现的这些显着影响。通过一个 最先进的成像、全细胞记录、光遗传学操作和高质量的结合 行为监测，我们将能够详细说明多个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。