Cholinergic contribution to pupil-linked arousal

摘要 胆碱能在瞳孔相关觉醒中的作用 行为状态，包括注意力和唤醒，对神经表征、知觉、 认知和行为表现，并由几个神经调节系统调节，包括 胆碱能系统和蓝斑-去甲肾上腺素系统。地球上的异常活动 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、帕金森氏病(PD)和抑郁症。非亮度调节的瞳孔大小的变化 几十年来，人们一直知道心理处理与潜在的行为是不同的。最近的研究强调了 瞳孔动力学能够跟踪大脑皮层觉醒状态的快速波动。因此，瞳孔大小的变化 在恒定光照下已被广泛用作非侵入性读出某些中枢的激活 唤醒回路与瞳孔大小有关，因此被用来索引与瞳孔相关的唤醒。非典型瞳孔动力学 在前述神经性疾病中都有报道。然而，调节的神经回路 与瞳孔有关的唤醒作用仍不清楚。拟议的项目将检验我们的中心假设：胆碱能 除了LC-NE系统外，其他系统也参与调节与瞳孔有关的觉醒。利用合成的光致发光剂 刺激、基因操作和钙成像，我们将在两个目标上检验这一假说。目标1将 确定胆碱能系统激活和瞳孔大小之间的因果联系。Aim 2将研究 通过瞳孔大小可以跟踪胆碱能活动的程度。这个项目将提供急需的洞察力 关于胆碱能系统在多大程度上促进了与瞳孔相关的觉醒。这样的信息是 对于使用瞳孔测量法对大量研究的结果进行严格和准确的解释至关重要，这是 在认知神经科学和精神病学中越来越普遍地使用。

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.