Determining the role of cortical acetylcholine in fast waking state transitions

摘要

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.