Noradrenergic and Cholinergic Mechanisms Underlying Pupil-Linked Arousal Modulation of Thalamic Sensory Processing

项目摘要 神经调节系统，包括蓝斑-去甲肾上腺素(LC-NE)系统(即去甲肾上腺素 系统)，对感官知觉和知觉行为产生重大影响。在感觉通路中， 丘脑处于战略地位，可以动态地控制信息流向大脑皮层。以前的工作有 证明了跨群体丘脑神经元的计时将信息流的性质切换到 而这种转换表现在知觉行为上。最近的研究表明，LC的激活 增加了单个丘脑中继神经元的特征选择性，这一改进归功于LC 丘脑中继核和丘脑网状核相互作用的调节。然而，如何 丘脑神经元对感觉信息的群体编码受LC-NE系统残存的调制 大部分都是未知的。LC是前脑去甲肾上腺素的主要来源，而 LC-NE系统与包括精神分裂症、帕金森氏病在内的主要临床疾病有关 阿尔茨海默病(PD)、注意力缺陷多动障碍(ADHD)和抑郁症。此外， 丘脑的异常活动被认为与大脑疾病有关，包括帕金森病、中枢性疼痛综合征、 和抑郁症。多样性补充项目将审查LC-NE系统对 触觉信号的丘脑群体编码。更具体地说，在清醒的丘脑中使用神经像素记录 与LC的化学发生刺激相一致，我们将1)表征各种不同类型的 丘脑中继区神经元的触觉信号特性，包括幅度、速度和方向等 核团和丘脑网状核在有无LC刺激的情况下，以及2)检查 丘脑群体对有无LC刺激的触觉检测表现的反应。这个项目将 提供关于LC-NE系统如何调节丘脑感觉处理的迫切需要的见解。是这样的 信息对于更好地了解神经系统疾病至关重要，在这些疾病中，异常的丘脑活动和 去甲肾上腺素能活性已有报道。

Project Summary Neuromodulatory systems, including the locus coeruleus – norepinephrine (LC-NE) system (i.e. noradrenergic system), exert heavy influences on sensory perception and perceptual behavior. In sensory pathways, the thalamus is strategically positioned to dynamically gate information flow to the cortex. Previous work has demonstrated that the timing across population thalamic neurons switched the nature of information flow to the cortex and the switch was manifested in perceptual behavior. More recent work showed that LC activation increased the feature selectivity of individual thalamic relay neurons, and this improvement was due to LC regulation of the interplay between the thalamic relay nucleus and thalamic reticular nucleus. However, how the population coding of sensory information by thalamic neurons is modulated by the LC-NE system remains mostly unknown. The LC is the primary source of norepinephrine to the forebrain, and the malfunction of the LC-NE system has been implicated in major clinical disorders, including schizophrenia, Parkinson’s disease (PD), Alzheimer’s disease, attention deficit hyper-activity disorder (ADHD), and depression. Moreover, abnormal activity in the thalamus has been implicated in brain disorders, including PD, central pain syndrome, and depression. The diversity supplement project will examine the influence of the LC – NE system on thalamic population coding of tactile signals. More specifically, using neuropixels recording in awake thalamus in concert with chemogenetic stimulation of the LC, we will 1) characterize the population coding of a variety of properties of tactile signals, including amplitude, velocity, and direction etc., for neurons in the thalamic relay nucleus and thalamic reticular nucleus with and without LC stimulation, and 2) examine the contribution of thalamic population response to tactile detection performance with and without LC stimulation. This project will provide much-needed insight about how the LC-NE systems modulates thalamic sensory processing. Such information is essential to better understand neurological disorders in which abnormal thalamic activity and noradrenergic activity have been reported.