Scientists have long known that the thalamus, a structure in the middle of the brain, was involved in arousal, but new research from the Wisconsin Institute for Sleep and Consciousness (WISC) identifies the sub-region that helps us wake up from sleep and anesthesia.
Lead authors Chiara Cirelli, MD, PhD, and Giulio Tononi, MD, PhD, used genetic tricks to show the important role of a specific brain region, the ventromedial nucleus (VM) of the thalamus, in helping us regain consciousness.
“These experiments are just one of a series of studies by several laboratories that should clarify the role of thalamic nuclei in the regulation of conscious states,” says Tononi, who directs the institute in the psychiatry department of the University of Wisconsin School of Medicine and Public Health. “This is now possible since genetic tools can target specific cell types in the thalamus in a selective and reversible way.”
The authors used techniques called optogenetics and chemogenetics, which use either a light signal or a specific drug, to turn on and off specially engineered cells in the brains of mice. In this case, the cells they targeted are matrix cells, which abound in the ventromedial nucleus.
They found that these cells are very active when we are awake and inactive during slow- wave sleep, which makes up most of sleep. They become active again during rapid eye movement sleep (REM), which is when we are most likely to experience dreams.
They also found that if these cells in mice are forced to fire during slow-wave sleep, when they are usually silent, the mouse wakes up in a matter of a few seconds. The same happens even when the mouse is deeply anesthetized and its brain shows slow waves similar to those present during slow-wave sleep. Thus, these results show that VM is a powerful “activating” system able to induce arousal.
“Another intriguing finding was that if we stimulated the VM matrix cells during REM sleep, when they are already active, the mouse does not wake up,” Cirelli notes. “This suggests that there must be other powerful mechanisms that keep us asleep while dreaming.”
Lead author Dr. Sakiko Honjoh has left UW for the University of Tsukuba International Institute for Integrative Sleep Medicine in Japan. Other authors are Shuntaro Sasai, Shannon S Schiereck and Hirotaka Nagai.
Funding for this research is from NIMH grant R01MH099231; NINDS grant P01NS083514; NIGMS grant R01GM116916; Tiny Blue Dot Inc. grant MSN196438/AAC1335; HFSP long-term fellowship LT000263/2012-L; and JSPS Overseas Research Fellowships.