Locus Coeruleus-Norepinephrine Modulation of Sensory Response and Tactile Perception

蓝斑-去甲肾上腺素（LC-NE）系统已被提出在以下方面具有关键作用： 调节认知行为，包括唤醒、感知和决策。然而，我们有有限的 了解LC-NE如何调节感知行为期间感觉处理的简单方面。 因此，在定量知觉行为中确定LC-NE的基本神经生物学是一个重要的研究课题。 这是理解它在调节高级认知功能和神经系统疾病中的作用的关键的第一步。 独特的是，我们已经克服了几个关键的技术限制，阻碍了基本的机制， 了解LC-NE功能。这些限制包括不能从化学定义的LC-1记录。 NE神经元在行为过程中，以及量化其对靶神经元的调节作用的困难。这 一项提案将测试中心假设，即LC-NE差异调节皮层兴奋性和抑制性 以促进感官知觉。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，因为它允许记录和扰动化学定义的LC-NE神经元， 同时监测他们的目标神经元在皮层，在定量知觉任务。这种方法 代表着对现状的实质性偏离。结合双电生理记录， 光遗传学获得/丧失功能，以及良好控制的行为，这种新的方法允许研究 在清醒行为的小鼠中的LC-NE调节的先前不可接近的机制。这项研究具有重要意义 因为它有望从根本上推进我们对LC-NE功能的理解， LC-NE对皮层感觉反应的调节与其对知觉反应的调节之间的机制联系 决策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。这些结果和新方法有可能帮助 更好地了解LC-NE在高级认知过程中的功能，并促进治疗性药物的开发 治疗神经系统疾病的方法。

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.