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.

项目摘要 神经调节系统，包括基因座 - 去甲肾上腺素（LC-NE）系统（即去甲肾上腺素能 系统），对感官感知和感知行为产生重大影响。在感官途径中 丘脑在战略上定位于动态的门信息流到皮层。以前的工作有 证明跨种群丘脑神经元的时机将信息流的性质切换到 皮质和开关以感知行为表现出来。最近的工作表明LC激活 提高了单个丘脑中继神经元的特征选择性，这种改善是由于LC引起的 调节丘脑继电器核与丘脑网状核之间的相互作用。但是，如何 丘脑神经元对感官信息的总体编码是由LC-NE系统调节的 主要是未知的。 LC是前脑去甲肾上腺素的主要来源，并且是故障 LC-NE系统已在包括精神分裂症，帕金森氏病在内的主要临床疾病中浸渍 （PD），阿尔茨海默氏病，注意力缺陷过度活跃障碍（ADHD）和抑郁症。而且， 丘脑中的异常活性已隐含在脑疾病中，包括PD，中央疼痛综合征， 和抑郁。多样性补充项目将检查LC - NE系统对 触觉信号的丘脑种群编码。更具体地说，在清醒的丘脑中使用Neuropixels录制 与LC的化学发生刺激一致，我们将1）表征多种多样的种群编码 触觉信号的属性，包括放大器，速度和方向等，用于丘脑继电器中的神经元 有和没有LC模拟的核和丘脑网状核，2）检查 丘脑种群对具有和没有LC刺激的触觉检测性能的反应。这个项目将 提供急需的有关LC-NE系统如何调节丘脑感官处理的见解。这样的 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 有报道了去甲肾上腺素的活性。