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

丘脑感觉处理的瞳孔相关唤醒调节的去甲肾上腺素能和胆碱能机制

• 批准号: 10836252
• 负责人: Qi Wang
• 金额: $ 9.32万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10836252
• 关键词: Alzheimer' s Disease; Arousal; Attention deficit hyperactivity disorder; Behavior; Brain Diseases; Cell Nucleus; Clinical; Code; Detection; Diagnosis; Disease; Genetic; Individual; Link; Mental Depression; Nature; Neurons; Norepinephrine; Parkinson Disease; Pathway interactions; Perception; Performance; Population; Positioning Attribute; Property; Prosencephalon; Pupil; Regulation; Reporting; Schizophrenia; Sensory; Signal Transduction; Source; System; Tactile; Thalamic structure; Work; awake; central pain syndrome; cholinergic; improved; insight; knowledge base; locus ceruleus structure; nervous system disorder; neuroregulation; noradrenergic; norepinephrine system; response

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.

项目概要 神经调节系统，包括蓝斑-去甲肾上腺素 (LC-NE) 系统（即去甲肾上腺素能 系统），对感官知觉和知觉行为产生重大影响。 丘脑的战略定位是动态控制流向皮质的信息流。 证明丘脑神经元群体的时序将信息流的性质转变为 最近的研究表明 LC 激活。 增加了单个丘脑中继神经元的特征选择性，这种改进归功于 LC 然而，丘脑中继核和丘脑网状核之间的相互作用是如何调节的。 丘脑神经元感觉信息的群体编码仍由 LC-NE 系统调节 LC 是前脑去甲肾上腺素的主要来源，而 LC 的功能障碍却是未知的。 LC-NE系统与主要临床疾病有关，包括精神分裂症、帕金森病 （PD）、阿尔茨海默病、注意力缺陷多动障碍（ADHD）和抑郁症。 丘脑的异常活动与大脑疾病有关，包括帕金森病、中枢性疼痛综合征、 多样性补充项目将研究 LC-NE 系统对抑郁症的影响。 更具体地说，使用清醒丘脑中的神经像素记录触觉信号的丘脑群体编码。 与 LC 的化学遗传学刺激相一致，我们将 1) 表征多种品种的群体编码 丘脑中继神经元触觉信号的特性，包括幅度、速度和方向等 核和丘脑网状核有和没有 LC 刺激，2) 检查 该项目将研究丘脑群体在有或没有 LC 刺激的情况下对触觉检测性能的反应。 提供有关 LC-NE 系统如何调节丘脑感觉处理的急需见解。 信息对于更好地了解神经系统疾病至关重要，其中丘脑活动异常和 去甲肾上腺素能活性已有报道。