Determining the role of cortical acetylcholine in fast waking state transitions

确定皮质乙酰胆碱在快速清醒状态转换中的作用

• 批准号: 10549356
• 负责人: ERIN NEYHART
• 金额: $ 4.77万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-08 至 2024-03-07
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10549356
• 关键词: Acetylcholine; Address; Affect; Age; Age Months; Alzheimer' s Disease; Animals; Area; Arousal; Automobile Driving; Behavior; Behavioral; Biosensing Techniques; Brain; Cell membrane; Cognitive; Cognitive deficits; Disease; Drowsiness; Exhibits; Fluorescence; Goals; Human Amyloid Precursor Protein; Image; Kinetics; Knowledge; Link; Locomotion; Measurement; Measures; Memory; Methodology; Miosis disorder; Mus; Muscarinic Acetylcholine Receptor; Mutation; Mydriasis; Neuromodulator; Neurons; Pattern; Performance; Population; Process; Pupil; Reporting; Role; Sensory; Somatosensory Cortex; Source; Specificity; Study models; System; Techniques; Technology; Testing; Time; Visual Cortex; Wakefulness; awake; basal forebrain; calcium indicator; cholinergic; constriction; extracellular; familial Alzheimer disease; information processing; insight; neural; neural patterning; neuromechanism; prevent; rate of change; response; sensor; visual processing; visual stimulus

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.

抽象的 大脑全天在各种状态之间自然过渡，这些大脑状态会影响 处理信息的方式。在清醒状态内有微妙的瞬态取代 在几秒钟的时间尺度上波动，并伴随着感觉处理的快速变化。通过获得 更好地理解这些赞助快速清醒状态过渡背后的机制，我们可能是 它可以在不同情况下解释更多大脑表现的可变性，并获得更多 详细了解如何产生不同信息处理方式。神经调节剂 由于乙酰胆碱（ACH）是众所周知的，在驱动定义不同大脑的神经模式中起作用 国家。但是，由于方法论的局限性，尚未确定ACH是否参与 在清醒内看到状态的快速变化。现在，最近的技术进步允许这些限制是 克服，我们旨在检验以下假设：皮质ACH确实参与了醒来状态的这些快速变化。 该项目的目的是确定何时以及何时可在皮质中起作用ACH与 国家的行为和神经签名，并研究这些疾病的可用性模式如何变化 州。特别是，该项目旨在确定赞成皮质ACH活性的空间量表 同质的，与基本前脑活动有关的ACH可用性的临时规模 赞助与脑状态神经特征有关的皮质ACH可用性波动，以及如何 在疾病状态下，ACH和行为特征之间的关系发生了变化。回答这些问题将 帮助我们通知我们的大脑状态如何出现并导致信息处理的变化以及填充 在有关神经调节剂可用性动力学方面的知识差距中。