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Director's Report

September 2021

The Connection Between Sleep Disturbances and Cardiometabolic Disorders

Congratulations to Huxing Cui, PhD, Assistant Professor of Neuroscience and Pharmacology and member of the FOEDRC, who is the recent recipient of a National Institutes of Health R01 grant.  Cui’s grant funded by the National Heart, Lung, and Blood Institute provides $2,267,270 through March of 2025.  The proposal is entitled:  “Decoding brain circuit underlying metabolic regulation of sleep-wake behavior”.

Sleep disorders and obesity are inextricably linked – poor sleep quality and short sleep duration increase the risk of developing obesity, while obesity is an independent risk factor for chronic sleep disruption (CSD) and excessive daytime sleepiness (EDS). Despite a clear bidirectional and pernicious association between obesity and sleep disorders, the brain pathways linking poor sleep and obesity are largely unknown. Dr. Cui’s research program seeks to identify critical neural circuits linking metabolic alterations to CSD and EDS. They recently discovered that a hormone secreted from fat cells called leptin, promotes wakefulness. Using sophisticated tools (chemogenetic activation) Cui demonstrated that when of a subset of GABAergic neurons in the lateral hypothalamic area (LHA) expressing leptin receptor (LepR) were activated, sleep was completely disrupted in mice. The overall objective of this research proposal is to clarify how leptin acts on key hypothalamic neurons to affect normal sleep-wake cycle.  His project will use the most advanced neuroscience techniques to answer these questions, including genetic manipulation, using light to target specific neurons with a technique known as optogenetics/chemogenetics, in vivo fiber photometry, and electrophysiology coupled with chronic wireless recording of EEG/EMG in freely moving animals. The proposed research is significant because it is expected to not only advance and our understanding of hypothalamic regulation of sleep-wake behavior but also shed light on largely unknown mechanisms that connect metabolic disorders to sleep-wake regulation. The proposed research is also innovative because it utilizes a combination of state-of-art neuroscience techniques coupled with sophisticated physiological measurements to address an important yet largely under-investigated question – what are the underlying neural circuits mediating CSD and EDS in obesity? Such knowledge may ultimately lead to the development of a novel strategy to effectively manage sleep problems associated with obesity in human patients.