Sleep Molecular Laboratory
The lab’s research strategy is to identify the neural circuitry responsible for the alternation between wake, sleep and REM sleep. Sleep and circadian rhythms of body temperature and activity are measured in rodents (rats and mice). Molecular (Dr. Meng Liu), pharmacological (Dr. Carlos Blanco-Centurion), anatomical (Dr. RodaRani Konadhode) and electrophysiology (Dr. Dheeraj Pelluru) methods are used to trace the network, record activity of neurons, identify gene expression in specific neuronal populations and whether destruction of specific neurons or loss of specific genes affects sleep. To destroy orexin receptor bearing neurons we created a novel compound linking saporin to the ligand orexin. This compound provides a rapid, cost effective method to test specific hypotheses regarding the role of specific brain regions in sleep-wake regulation. Once it is found that loss of a gene or neurons results in a sleep abnormality then novel methods are used to repair the network and determine whether sleep returns to normal. Recently, we demonstrated the first ever use of gene transfer to treat a sleep disorder. Our most recent study identified an hitherto unknown group of neurons in the subthalamus that control cataplexy, an important symptom of narcolepsy (Liu et al., J Neuroscience, 2011).
The primary focus of the research is on the sleep disorder, narcolepsy. Dr. Shiromani’s research career was started in 1986 by a small grant from the American Narcolepsy Association. Since then the laboratory has been continuously funded by the NIH, the VA and the DoD.
This lab provides training in long-term (months) recording of sleep and circadian rhythms in rodents. Dr. Shiromani has trained many students who have now established their own labs. Training is also provided in molecular biology, immunohistochemistry, microdialysis, HPLC and single cell recording of neurons in freely-behaving rodents.