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Cholinergic contribution to pupil-linked arousal

胆碱能对瞳孔相关唤醒的贡献

基本信息

批准号：
10301014
负责人：
Qi Wang
金额：
$ 20.25万
依托单位：
COLUMBIA UNIV NEW YORK MORNINGSIDE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-11-11 至 2023-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10301014
关键词：
Ablation Affect Arousal Attention Attention deficit hyperactivity disorder Behavior Behavior Therapy Behavioral Belief Brain Brain Diseases Brain Stem Calcium Cell Nucleus Clinical Cognition Data Development Diagnosis Disease Fluorescence Goals Head Health Image Individual Knowledge Lighting Link Measures Mediating Mental Depression Mental disorders Mus Mydriasis Neurons Norepinephrine Outcome Parkinson Disease Pathologic Pedunculopontine Tegmental Nucleus Perception Performance Persons Population Process Psyche structure Psychiatry Psychology Publishing Pupil Reporting Role Schizophrenia Sensory Signal Transduction System Testing Thalamic structure Viral Vector Work awake basal forebrain base behavioral impairment calcium indicator cholinergic cognitive neuroscience common symptom cost experimental study genetic manipulation improved indexing information processing insight knowledge base locus ceruleus structure luminance nervous system disorder neural circuit neuropsychiatric disorder neuroregulation norepinephrine system offspring optogenetics rapid growth relating to nervous system response tool translational impact

项目摘要

Abstract Cholinergic contribution to pupil-linked arousal Behavioral state, including attention and arousal, exerts heavy influences on neural representation, perception, cognition, and behavioral performance and is regulated by several neuromodulatory systems, including the cholinergic systems and the locus coeruleus-norepinephrine (LC-NE) system. Abnormal activity in the cholinergic systems has been implicated in major clinical disorders that affect millions of people, including schizophrenia, Parkinson’s disease (PD), and depression. Non-luminance mediated changes in pupil size have been known to co-vary with mental processing underlying behavior for decades. Recent work highlighted that pupil dynamics were able to track rapid fluctuation of cortical arousal state. Therefore, change in pupil size under constant illumination has been widely used as a non-invasive readout of the activation of certain central arousal circuits related to pupil size, and thus is used to index pupil-linked arousal. Atypical pupil dynamics have been reported in the aforementioned neurological disorders. However, the neural circuits that mediate pupil-linked arousal remain unclear. The proposed project will test our central hypothesis: the cholinergic systems mediate pupil-linked arousal, in addition to the LC-NE system. Using a synthesis of optogenetic stimulation, genetic manipulation, and calcium imaging, we will test this hypothesis in two Aims. Aim 1 will determine the causal link between activation of the cholinergic systems and pupil size. Aim 2 will examine the extent to which cholinergic activity can be tracked by pupil size. This project will provide much-needed insight about the extent to which the cholinergic systems contribute to pupil-linked arousal. Such information is essential to rigorous and accurate interpretation of results from numerous studies using pupillometry, which is increasingly popularly used in cognitive neuroscience and psychiatry.

抽象的胆碱能对瞳孔相关唤醒的贡献行为状态，包括注意力和唤醒，对神经表征、感知、认知和行为表现，并受到多种神经调节系统的调节，包括胆碱能系统和蓝斑去甲肾上腺素（LC-NE）系统。异常活动胆碱能系统与影响数百万人的重大临床疾病有关，包括精神分裂症、帕金森病（PD）和抑郁症。非亮度介导的瞳孔大小变化几十年来，人们都知道它与潜在行为的心理处理共同变化。最近的工作强调了瞳孔动态能够追踪皮质唤醒状态的快速波动。因此，瞳孔大小的变化在恒定照明下已被广泛用作某些中枢激活的非侵入性读数唤醒电路与瞳孔大小相关，因此用于索引与瞳孔相关的唤醒。非典型瞳孔动态在上述神经系统疾病中已有报道。然而，介导的神经回路与瞳孔相关的唤醒仍不清楚。拟议的项目将测试我们的中心假设：胆碱能除了 LC-NE 系统之外，系统还介导与瞳孔相关的唤醒。利用光遗传学综合刺激、基因操作和钙成像，我们将在两个目标中检验这一假设。目标1将确定胆碱能系统的激活与瞳孔大小之间的因果关系。目标 2 将检查通过瞳孔大小可以追踪胆碱能活动的程度。该项目将提供急需的见解关于胆碱能系统对瞳孔相关唤醒的贡献程度。此类信息是对于使用瞳孔测量法进行大量研究的结果进行严格和准确的解释至关重要，这是越来越广泛地应用于认知神经科学和精神病学。