Locus Coeruleus-Norepinephrine Modulation of Sensory Response and Tactile Perception

蓝斑-去甲肾上腺素对感觉反应和触觉感知的调节

• 批准号: 9894870
• 负责人: Hongdian Yang
• 金额: $ 33.16万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-15 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9894870
• 关键词: Affect; Arousal; Attention; Behavior; Behavioral; Brain; Chemicals; Clinical; Cognitive; Data; Decision Making; Detection; Disease; Electrophysiology (science); Goals; Interneurons; Knowledge; Link; Measures; Membrane Potentials; Mental Depression; Methods; Mission; Monitor; Mus; Neurobiology; Neurons; Neurosciences; Norepinephrine; Parvalbumins; Perception; Performance; Public Health; Regulation; Research; Role; Sensory; Somatosensory Cortex; Source; System; Tactile; Task Performances; Techniques; Testing; United States National Institutes of Health; Whole-Cell Recordings; anxiety-related disorders; awake; behavior influence; behavioral outcome; cognitive function; cognitive process; extracellular; hippocampal pyramidal neuron; information processing; innovation; insight; locus ceruleus structure; loss of function; nervous system disorder; neuromechanism; neuroregulation; norepinephrine system; novel; novel strategies; novel therapeutic intervention; optogenetics; relating to nervous system; response; therapeutic development

The locus coeruleus-norepinephrine (LC-NE) system has been proposed to have a critical role in regulating cognitive behavior, including arousal, perception, and decision making. However, we have limited understanding of how LC-NE modulates even simple aspects of sensory processing during perceptual behavior. Therefore, determining the fundamental neurobiology of LC-NE during quantitative perceptual behavior is a crucial first step toward understanding its role in modulating higher cognitive functions and neurological disorders. Uniquely, we have overcome several key technical limitations which have impeded fundamental mechanistic understanding of LC-NE functions. These limitations include the inability to record from chemically-defined LC- NE neurons during behavior, and the difficulty of quantifying their modulatory effects on target neurons. This proposal will test the central hypothesis that LC-NE differentially modulates cortical excitatory and inhibitory responses to facilitate sensory perception. We will determine: How does LC-NE influence behavioral outcomes? How does LC-NE modulate neuronal activity in the primary somatosensory cortex? The proposed research is innovative, in our opinion, because it allows recording and perturbing chemically-defined LC-NE neurons while simultaneously monitoring their target neurons in the cortex, during a quantitative perceptual task. This approach represents a substantive departure from the status quo. Combining dual-electrophysiological recordings, optogenetic gain-/loss-of-function, and well-controlled behavior, this novel approach allows investigating previously inaccessible mechanisms of LC-NE modulation in awake behaving mice. The research is significant because it is expected to fundamentally advance our understanding of LC-NE functions by establishing mechanistic links between LC-NE modulation of cortical sensory response and its modulation of perceptual decisions. The new techniques can be adapted to other neuromodulatory systems, and are expected to contribute to a broader understanding of brain functions. The results and new methods have the potential to help better understand LC-NE functions in higher cognitive processes, and to facilitate the development of therapeutic methods to treat neurological disorders.

蓝斑-去甲肾上腺素 (LC-NE) 系统被认为在 调节认知行为，包括唤醒、感知和决策。然而我们的能力有限 了解 LC-NE 在感知行为过程中如何调节感觉处理的简单方面。 因此，确定定量知觉行为期间 LC-NE 的基本神经生物学是一个 理解其在调节高级认知功能和神经系统疾病中的作用至关重要的第一步。 独特的是，我们克服了几个阻碍基本机制的关键技术限制 了解 LC-NE 功能。这些限制包括无法从化学定义的 LC 中进行记录 NE 神经元在行为过程中的作用，以及量化它们对目标神经元的调节作用的困难。这 该提案将检验 LC-NE 差异调节皮质兴奋性和抑制性的中心假设 促进感官知觉的反应。我们将确定：LC-NE 如何影响行为结果？ LC-NE 如何调节初级体感皮层的神经元活动？拟议的研究是 我们认为这是创新的，因为它允许记录和扰动化学定义的 LC-NE 神经元，同时 在定量感知任务中同时监测皮质中的目标神经元。这种做法 代表着对现状的实质性背离。结合双电生理记录， 光遗传学功能获得/丧失以及良好控制的行为，这种新颖的方法允许研究 此前在清醒行为小鼠中无法实现的 LC-NE 调节机制。研究意义重大 因为通过建立 皮质感觉反应的 LC-NE 调节与其知觉调节之间的机制联系 决定。这些新技术可以适用于其他神经调节系统，并有望 有助于更广泛地了解大脑功能。结果和新方法有可能提供帮助 更好地了解 LC-NE 在高级认知过程中的功能，并促进治疗方法的开发 治疗神经系统疾病的方法。