The ability to control arousal is essential to modern medicine, with broad applications in anesthesia, sleep medicine and psychiatry. However, arousal control is not binary, but rather involves the complex orchestration of multiple neuromodulatory circuits. The Li Lab therefore aims to better understand the neurobiology of these neuromodulatory circuits across broad spatiotemporal scales, integrating findings at the molecular, synaptic, circuit, physiological and behavioral levels. We also adapt technology to enable bidirectional modulation of arousal with increased circuit-specificity. The long-term goal is to control arousal more precisely via rational targeting of specific neural circuits.
Research Projects
Logic of neuromodulatory circuits in arousal
We examine how specific projections of neuromodulatory circuits and neuromodulatory circuits in combination affect arousal.
Neuromodulatory circuits are important in controlling arousal and are often co-opted in medicine to alter a patient’s arousal level, but how they work in concert is not well known. We use a rich repertoire of cutting-edge techniques in a small-animal model, such as single-cell RNA sequencing, tissue clearing for anatomical mapping, fiber photometry, silicone probe recording and machine learning to determine how different arousal circuits interact. In particular, we have a strong focus on the locus coeruleus, an important noradrenergic circuit that can couple its arousal function to other important brain processing and physiological functions.
Opioid systems in arousal modulation
We examine how different opioid systems modulate arousal and their potential translation in sleep disorders.
The opioid epidemic claimed more than 80,000 lives in 2022 and remains a heavy economic burden in society. We aim to understand how chronic opioid use and withdrawal can disrupt sleep via the locus coeruleus, an important noradrenergic output of the brain, as poor sleep is associated with continued opioid use and relapse. We also are interested in the nociceptin opioid receptor (NOPR) system, with minimal cross-reactivity to the other opioid receptors. As NOPR activation can lead to sedation, we characterize this sedation and seek to find out the brain circuits that may underlie this effect on arousal.
Tool development in arousal modulation
We collaborate with others to develop tools to modulate arousal bidirectionally.
We are interested in using focused ultrasound to develop a non-invasive, non-pharmacological way of modulating arousal.
Publications
Li L, Rana A*, Li EM*, Feng J, Li Y, and Bruchas MR. Activity-dependent constraints on catecholamine signaling. (2023) Cell Rep. 42(12):113566. PMID: 38100349. *Equal contribution
Luskin AT*, Li L*, Fu X, Barcomb K, Blackburn T, Li EM, Rana A, Simon RC, Sun L, Murry A, Golden SA, Stuber GD, Ford CP, Gu L, and Bruchas MR. A diverse network of pericoerulear neurons control arousal states. BioRxiv [Preprint] https://doi.org/10.1101/2022.06.30.498327. *Equal Contribution
Li L, Rana AN*, Li EM*, Travis MO, Bruchas MR. Noradrenergic tuning of arousal is coupled to coordinated movements. BioRxiv [Preprint] https://doi.org/10.1101/2024.06.18.599619. *Equal Contribution
See a full list of Dr. Li's publications at PubMed
Join the Lab
We are looking for motivated individuals with eclectic backgrounds who can bring new approaches to solving problems in arousal neurobiology and consciousness. Please email Dr. Li with your CV and cover letter.