Determining the role of cortical acetylcholine in fast waking state transitions

摘要 大脑在一天中自然地在各种状态之间转换，这些大脑状态会影响大脑的功能。 信息处理的方式。在清醒状态中，有一些微妙的、短暂的子状态， 以秒为单位波动，并伴随着感官处理的快速变化。通过获得 更好地理解这些自发的快速清醒状态转换背后的机制，我们可能会 能够解释大脑在不同情况下表现的更多变化，并获得更多 详细了解如何产生不同的信息处理模式。神经调节剂， 众所周知，乙酰胆碱（ACh）在驱动定义不同大脑的神经模式中发挥作用 states.然而，由于方法学的限制，尚未确定ACh是否参与了 在清醒状态下看到的快速变化。现在，最新的技术进步允许这些限制， 克服，我们的目标是测试的假设，皮质乙酰胆碱确实参与了这些快速转变清醒状态。 该项目的目标是确定ACh在何时何地作用于大脑皮层， 状态的行为和神经特征，并研究这些可用性模式如何在疾病中变化 状态具体来说，该项目旨在确定自发皮质ACh活动的空间尺度， 同质，乙酰胆碱的可用性与基底前脑活动的时间尺度， 自发波动的皮质ACh可用性与大脑状态的神经特征有关，以及 ACh和行为特征之间的关系在疾病状态下改变。回答这些问题将 帮助我们了解不同的大脑状态是如何产生的，并导致信息处理的变化，以及填充 关于神经调节剂可用性动力学的知识缺口。

ABSTRACT The brain naturally transitions between a variety of states throughout the day, and these brain states affect the way information is processed. Within the state of wakefulness there are subtle, transient substates which fluctuate on a seconds-long timescale and are accompanied by rapid changes in sensory processing. By gaining a better understanding of the mechanism behind these spontaneous fast waking state transitions, we may be able to explain more of the variability in the brain’s performance under different circumstances, and gain more detailed insight into how different modes of information processing are being produced. Neuromodulators such as acetylcholine (ACh) are well-known to play a role in driving the neural patterns which define distinct brain states. However, due to limitations in methodology, it has yet to be determined whether ACh is involved in the fast shifts in state seen within wakefulness. Now that recent technological advances allow these limitations to be overcome, we aim to test the hypothesis that cortical ACh is indeed involved in these fast shifts in waking states. The goal of this project is to determine when and where ACh is available to act in the cortex in relation to behavioral and neural signatures of state, and investigate how these patterns of availability change in a disease state. Specifically, this project aims to determine the spatial scale at which spontaneous cortical ACh activity is homogeneous, the temporal scale of ACh availability in relation to activity of the basal forebrain, how patterns of spontaneously fluctuating cortical ACh availability relate to neural features of brain state, and how the relationship between ACh and behavioral features is altered in a disease state. Answering these questions will help to inform us how different brain states arise and lead to variability in information processing, as well as fill in knowledge gaps regarding the dynamics of neuromodulator availability in general.