BLR&D Research Career Scientist Award Application for Priyattam J. Shiromani, PhD

Ralph H Johnson Va Medical Center, Charleston SC

Investigators

Linked publications & trials

Abstract

70 million Americans suffer from some sort of sleep disorder. Behavior, mood and memory deteriorate with sleep loss and it gets worse with continuing sleep deprivation. Sleep disturbance is a frequent and common complaint among our Veterans. Lack of sleep due to hyperarousal is one symptom of PTSD, but it is not known why Veterans with PTSD cannot fall asleep. My research focuses on identifying and mapping the brain neurons that induce sleep. The overall impact of my research is that it will provide the first direct evidence linking specific phenotypes of neurons and their circuits responsible for inducing sleep. This will make it possible to induce sleep in conditions where the arousal drive is very strong, such as in the insomnia of PTSD, or to maintain wakefulness when there is excessive sleepiness, such as in patients with obstructive sleep apnea or atypical depression. I employ deep-brain imaging, optogenetics and CLARITY to identify functional circuits in the brain. The brain contains many different types of cells but with the new tools it is possible to disassemble the brain to identify the culprit neurons responsible for complex behaviors, such as sleep. With the miniscope, we have gathered the largest database of neurons in the brain (~1000 neurons; 4 phenotypes; MCH, GABA, Lhx6 and dynorphin) that show activity linked specifically to sleep. As proof, we mechanistically (optogenetics) activated only a few neurons in one small area of the hypothalamus in one brain hemisphere and discovered that it shifted a waking brain to sleep. Other investigators are demonstrating that behaviors such as speech, movement, vision can be triggered by activating small circuits in the brain. My intent is to restore normal sleep when the circuit is affected by disease or trauma. Overall, these neuroscience methods and tools aid the collective research effort at RHJVAMC. My experience guides the junior faculty towards independence.