Noradrenergic modulation of sensory perception

摘要 相同的感官刺激可以被感知或忽略，这取决于任务参与的水平， 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 同样的刺激？上行神经调质去甲肾上腺素（NE），主要由小的 脑干蓝斑核（LC），已被提出在调节多个方面具有关键作用 包括感知、注意力和决策。在本提案中，我们假设， LC活动的两种不同模式（紧张性对相位性）差别地调节感觉知觉。通过组合 多通道细胞外记录和LC活性的光遗传学扰动， 下游大脑区域，以及良好控制的行为，我们将评估LC活动的不同模式 调节感觉处理和知觉决定。利用小鼠的感觉检测任务，我们将 确定：1）LC-NE活动如何影响感知行为表现？2)如何LC滋补和 阶段性活动相关？3)LC-NE活动如何调节皮层感觉加工？拟议 在我们看来，这项研究是创新的，因为它允许我们记录和干扰LC中NE释放神经元， 同时监测其下游神经元在皮质中的活动， 知觉行为结合LC及其下游脑区的双重电生理记录， 精确的光遗传学操作和良好的控制行为，我们希望提供新的方法来获得 LC-NE功能的基本知识。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提供机械的见解， 知觉行为和认知功能障碍的神经调节，可能促进 注意力和焦虑相关疾病的新疗法。

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.