Research

The primary objective of our lab is to unveil the mystery of sleep and dreams through multidisciplinary research approaches. We pursue three major research directions: (1) the function and regulation of sleep, (2) the interplay between sleep and neurodegenerative diseases, and (3) the implemention of artificial intelligence in sleep research.

The Theory of Sleep: Self-Cleansing Brain Hypothesis
We believe that one primary function of sleep is to restore metabolic homeostasis. Excess waste produced by neuronal activity during wakefulness generates the drive to sleep, while the function of sleep is to remove these harmful wastes, ensuring optimal brain performance. Our recent research has discovered that neurons synchronize their activity during sleep to create large-amplitude and rhythmic ionic currents (waves) in the brain interstitial fluid. These waves power fluid flow, effectively clearing metabolic waste from the brain. We summarize this principle as, neurons that fire together shower together. In light of this foundational concept, we aim to investigate how neural circuits are shaped by the demand for self-cleansing throughout the evolution of sleep.

Sleep and Neurodegeneration: The Intricate Dialogue Between Sleep and Protein Metabolism
The pathological accumulation of several endogenous proteins (such as amyloid-beta, tau, and alpha-synuclein) in the brain is a hallmark of numerous neurodegenerative diseases, and sleep has been increasingly implicated in both the onset and progression of Alzheimer's disease (AD). In particular, declining sleep quality has emerged as a major risk factor for aging-associated cognitive decline and the development of AD. Although there is growing consensus regarding the influence of sleep on AD, the mechanisms by which sleep confers neuroprotection remain a topic of intense debate. Leveraging systems neuroscience toolkits and metabolic techniques, we aims to uncover how neuronal dynamics and sleep regulate the metabolism of the disease-associated proteins.

Here are a few research directions we are currently pursuing:

  1. Recording and visualizing neural activity and brain interstitial fluid dynamics across different brain states.
  2. Identifying the macroscale circuitry organizing global fluid perfusion and molecular clearance.
  3. Pinpointing the micro-circuitry orchestrating local fluid perfusion and brain clearance.
  4. Determining how neural dynamics regulate the metabolism of endogenous disease-associated proteins.
  5. Implementing sleep mechanisms in artificial neural networks.