Locus Coeruleus-Norepinephrine Modulation of Sensory Response and Tactile Perception

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，我们已经限制了 了解LC-NE如何在知觉行为中调节感觉处理的简单方面。 因此，在定量知觉行为过程中确定LC-NE的基础神经生物学是一项 了解它在调节高级认知功能和神经紊乱中的作用的关键的第一步。 独一无二的是，我们克服了几个关键的技术限制，这些限制阻碍了基本机械 了解LC-NE功能。这些限制包括无法从化学定义的LC记录- 行为过程中的NE神经元，以及量化它们对靶神经元的调制作用的难度。这 提案将检验LC-NE差异性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如何调节初级躯体感觉皮层的神经元活动？拟议的研究是 创新，在我们看来，因为它允许记录和干扰化学定义的LC-NE神经元，同时 在一项定量知觉任务中，同时监测它们在大脑皮层的目标神经元。这种方法 代表着与现状的实质性背离。结合双电生理记录， 光遗传功能的增减，以及良好控制的行为，这种新的方法允许研究 清醒行为小鼠的LC-NE调节机制以前是不可知的。这项研究具有重要意义 因为它有望从根本上促进我们对LC-NE功能的理解 大脑皮层感觉反应的LC-NE调节与知觉调节的机制联系 决定。这项新技术也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。研究结果和新方法有可能对我们有所帮助。 更好地了解LC-NE在高等认知过程中的作用，促进治疗的发展 治疗神经性疾病的方法。

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.