Identifying biological signals that change between sleep and wakefulness

Mentor: Yao Chen, Assistant Professor of Neuroscience, Cell Biology and Physiology, and Biomedical Engineering

Lab description: Neuromodulators such as dopamine, acetylcholine, and neuropeptides have profound effects on neural circuits and behavior. Altered neuromodulation is associated with most psychiatric disorders, major neurodegenerative disorders, and neuromodulatory systems are targets of almost all drugs of abuse. While specific behaviors have been linked to specific neuromodulators, and while many neuromodulator receptors and their downstream signaling pathways are known, how neuromodulators regulate behavior remains enigmatic.

The knowledge gap exists because our understanding of molecular signaling networks remains largely a static diagram of connections between molecules. Our laboratory attempts to fill the gap between molecular neuroscience and animal behavior by elucidating the spatial and temporal dynamics of biological signals, because their dynamics carry critical information that explain subsequent modifications of cells, circuits, and behavior.

Specifically, we aim to understand how the dynamics of neuromodulators and intracellular signals contribute to the function of neuromodulators, to learning, and to the function of sleep. We combine biosensor development, two photon fluorescence lifetime imaging microscopy, electrophysiology, as well as molecular, cellular, and biochemical approaches in mice to visualize molecular dynamics in action, perturb them with precise spatiotemporal control, and analyze the functional consequences. Our research promises to uncover principles of neuromodulator action, illuminate how molecular mechanisms produce behaviorally relevant features, and ultimately help treat psychiatric disorders.

Project: Despite the importance of sleep, it is unclear how sleep promotes many important functions (e.g. cardiovascular health, emotions, learning, immune functions). We will use fluorescence lifetime photometry combined with EEG/EMG analysis to identify biological signals that change between sleep and wakefulness. They will immediate generate hypotheses on the cellular functions of sleep. The student interested in this project needs to be comfortable handling live mice, detail oriented, and not afraid of new technology/software. The student will receive extensive mentoring and support.