Noradrenergic modulation of sensory perception

感觉知觉的去甲肾上腺素能调节

• 批准号: 9797280
• 负责人: Hongdian Yang
• 金额: $ 33.23万
• 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: 2019-05-15 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9797280
• 关键词: Affect; Anxiety; Area; Arousal; Attention; Awareness; Behavior; Behavioral; Brain; Brain Stem; Brain region; Cell Nucleus; Clinical; Cognition Disorders; Cognitive; Data; Decision Making; Detection; Development; Disease; Electrophysiology (science); Goals; Human; Impaired cognition; Knowledge; Link; Measures; Membrane Potentials; Methodology; Methods; Mission; Monitor; Mus; Neurobiology; Neuromodulator; Neurons; Neurosciences; Norepinephrine; Pattern; Perception; Performance; Phase; Population; Process; Public Health; Regulation; Research; Role; Sensory; Somatosensory Cortex; Source; Spike Potential; Stimulus; System; Tactile; Task Performances; Techniques; United States National Institutes of Health; Whole-Cell Recordings; anxiety-related disorders; behavioral outcome; cognitive function; cognitive process; extracellular; innovation; insight; locus ceruleus structure; neglect; nervous system disorder; neuroregulation; nonhuman primate; noradrenergic; novel; novel strategies; optogenetics; patch clamp; prevent; relating to nervous system; response; sensory cortex; sensory stimulus

ABSTRACT Identical sensory stimuli can be perceived or neglected, depending on the level of task engagement or brain states. What are the underlying neural processes that influence our awareness of the presence or absence of the same stimulus? The ascending neuromodulator norepinephrine (NE), arising mainly from a small brainstem nucleus locus coeruleus (LC), has been proposed to have a critical role in regulating multiple aspects of cognitive behavior, including perception, attention and decision-making. In this proposal, we hypothesize that the two distinct modes of LC activity (tonic vs. phasic) differentially modulate sensory perception. By combining multi-channel extracellular recording and optogenetic perturbation of LC activity, patch-clamp recording in the downstream brain region, and well-controlled behavior, we will assess how different patterns of LC activity modulate sensory processing and perceptual decisions. Capitalizing on a sensory detection task in mice, we will determine: 1) How does LC-NE activity influence perceptual behavior performance? 2) How are LC tonic and phasic activity related? 3) How does LC-NE activity modulate cortical sensory processing? The proposed research is innovative, in our opinion, because it allows us to record and perturb NE-releasing neurons in the LC simultaneously with monitoring the activity of their downstream neurons in the cortex during quantitative perceptual behavior. Combining dual-electrophysiological recordings in the LC and its downstream brain area, precise optogenetic manipulation, and well-controlled behavior, we expect to offer novel approaches to acquiring fundamental knowledge of LC-NE functions. The new techniques can be readily adapted to other brain circuits and their downstream targets, and thus are expected to contribute to a broader understanding of neuromodulation and brain functions. The knowledge gained is expected to provide mechanistic insights into neuromodulation of perceptual behavior and cognitive dysfunctions, potentially facilitating the development of new treatments for attention- and anxiety-related disorders.

抽象的 相同的感官刺激可能会被感知或忽略，具体取决于任务参与程度或 大脑状态。影响我们对存在或不存在的意识的潜在神经过程是什么 相同的刺激？上行神经调节剂去甲肾上腺素 (NE)，主要由小分子产生 脑干蓝斑核（LC）被认为在调节多个方面具有关键作用 认知行为，包括感知、注意力和决策。在这个提案中，我们假设 LC 活动的两种不同模式（强直性与阶段性）对感官知觉有不同的调节作用。通过结合 LC 活性的多通道细胞外记录和光遗传学扰动，膜片钳记录 下游大脑区域和良好控制的行为，我们将评估 LC 活动的不同模式如何 调节感觉处理和知觉决策。利用小鼠的感官检测任务，我们将 确定：1) LC-NE 活动如何影响知觉行为表现？ 2) LC补品如何？ 阶段性活动相关？ 3) LC-NE 活性如何调节皮质感觉处理？拟议的 我们认为，这项研究具有创新性，因为它使我们能够记录和扰动 LC 中释放 NE 的神经元 同时在定量过程中监测皮层下游神经元的活动 感性行为。结合 LC 及其下游脑区的双电生理记录， 精确的光遗传学操作和良好控制的行为，我们期望提供新的方法来获取 LC-NE 功能的基础知识。新技术可以很容易地适应其他大脑回路 及其下游目标，因此有望有助于更广泛地了解 神经调节和大脑功能。所获得的知识预计将为以下方面提供机械见解： 知觉行为和认知功能障碍的神经调节，可能促进 针对注意力和焦虑相关障碍的新疗法。