Markus H. Schmidt, MD, PhD joined the Inselspital and the University of Bern in 2015 as Oberartz specializing in sleep medicine in the Schlaf-Wach-Epilepsie-Zentrum (SWEZ) after coming from the United States. As a group leader in the Zentrum for Experimental Neurology (ZEN), he holds a unique position in both clinical and animal research.
Dr. Schmidt has developed a new theory on the function of sleep known as the energy allocation (EA) hypothesis (Schmidt, 2014). Prior theories on sleep as an energy conservation strategy have focused only on metabolic rate reduction during sleep, similar in concept to hibernation. Sleep, however, is a highly active process where unique biological functions become upregulated compared to wake, including protein synthesis, intracellular transport, membrane repair, memory consolidation and immune function, to name a few. The EA hypothesis proposes that sleep-wake cycling promotes energy conservation through state-dependent metabolic partitioning as a means of promoting resource optimization (Schmidt, 2014; Latifi et al, 2018). Using mathematical modeling, Schmidt suggests that the partitioning of functions by behavioral state at the whole organism level conserves more energy than previously thought, elucidating why all species of the animal kingdom sleep (Schmidt et al., 2017).
Since arriving in Bern, his work has focused on testing predictions of the EA hypothesis, particularly with respect to the role of rapid eye movement (REM) sleep. In addition to muscle atonia, rapid eye movements, twitching of the extremities and an increase in brain metabolic activity which characterize this state, REM sleep is also associated with a loss of thermoregulatory control. The EA hypothesis proposes that REM sleep is opportunistically expressed when the need for thermoregulatory defense is minimized. His hypothesis predicts the presence of neural mechanisms to dynamically modulate REM sleep expression as a function of ambient temperature (Ta). Employing optogenetics and genetically engineered mice, his prediction was confirmed with the finding that the melanin-concentrating (MCH) neurons within the lateral hypothalamus drive REM sleep when sleeping in a warm thermoneutral Ta (Komagata et al, 2019).
Dr. Schmidt is also exploring the neural mechanisms of REM sleep and cataplexy. Cataplexy is a sudden loss of muscle tone triggered by positive emotions in the disorder narcolepsy. Using Ta manipulation in narcoleptic mice, his group has discovered that REM sleep and cataplexy can be dissociated (Viberti et al., 2021), identifying a new model to dissect their underlying neural mechanisms. This work includes optogenetics and calcium imaging in a narcolepsy mouse model.