Robust circuit computation in freely behaving animals.

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Project Summary/Abstract Sleep is necessary for all brain function and ultimately life. The core function by which sleep contributes to healthy cognition remains one of the great questions facing neuroscience. Recent theories point to powerful cellular rules, but these are controversial and have difficulty accounting for the effects of sleep in ethologically and developmentally diverse circumstances. We recently showed that cortical circuit dynamics are actively tuned to criticality, a computational regime that maximizes information processing. This regime is disrupted by changes in synaptic strength, such as those believed to typify waking experience. This raises the intriguing possibility that the core mechanism by which sleep benefits neural function is by restoring criticality. Our preliminary experiments support this hypothesis. The overall goal of this project is to develop a new framework for understanding the neural impact of sleep and experience at the level of network dynamics. We will continuously track 500-1000 single neurons in the brains of freely behaving animals for up to six months. We will track sleep, wake, behavior, and neural dynamics across the entire distribution of naturally occurring behavior. We will take advantage of this methodologically integrated approach to understand how circuits in the brain maintain the stable computation necessary for cognition and natural behavior on long time-scales. In Aim 1, we will test the relationship between specific classes of behavior and criticality in underlying networks. In Aim 2, we will test the impact of wake and sleep on criticality across the brain for the majority of an animal's lifetime. In Aim 3, we will use a modelling-based approach to establish the mechanisms of criticality in the intact brain. The results of this work will shed light on a long-standing gap in our knowledge of fundamental neurobiology. Given the increasingly recognized role of sleep in a vast number of brain-related disorders, an understanding of how sleep works will open the door to significant health-related progress in the future. This work directly advances the mission of the BRAIN Initiative.