Circuit control of REM sleep

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Understanding how the brain controls REM sleepREM sleep is one of the three fundamental behavioural states experienced by mammals, birds and reptiles (wakefulness and non-REM sleep are the other two). REM sleep is characterized by vivid dreaming, cortical activation and skeletal muscle paralysis, and is important for nervous system development, brain cell function, memory consolidation and certain forms of learning. Science magazine identified how and why we dream during REM sleep as being one of the 100 most important, but unanswered questions, in science. But, despite more than 6 decades of research it still remains unclear how the brain generates REM sleep. One reason for the limited progress in identifying how the brain controls REM sleep stems from the technical limitations associated with conventional science tools. However, new technologies called optogenetics and chemogenetics are now making it possible to study the brain circuits that turn REM sleep on and off. The goal of this NSERC research is to identify the core brain circuits that control REM sleep in mice using cutting-edge optogenetic and chemogenetic strategies. REM sleep is important for normal animal physiology, and is a unique behavioural state characterized by hippocampal theta activity (which is an important type of brain-wave that promotes learning) and skeletal muscle paralysis. However, the mechanisms that switch REM sleep on and off and that produce its defining features (theta activity and muscle atonia) remain poorly understood. The objectives of this proposal are to: 1) Identify the core brain circuits that generate REM sleep. 2) Determine which circuits function to terminate periods of REM sleep. 3) Define the circuits that induce hippocampal theta activity and muscle atonia during REM sleep.Our goal is to study the brain cells that control REM sleep using the latest and most precise tools in science, called optogenetics and chemogenetics. These tools are important for understanding how the brain controls REM sleep because they allow us to rapidly turn specific brain cells “on” and “off” so that their roles in producing REM sleep can be accurately determined. For example, if a particular type of brain cell is involved in producing REM sleep then switching it “off” should prevent REM sleep and switching in “on” should cause REM sleep. These experiments will therefore allow us to carefully study and identify how the cell circuits in a mouse's brain produce REM sleep. These experiments are important to biology and medicine because they will advance our understanding of how the brain controls REM sleep, which will allow biologists to better understand the natural functions of REM sleep and will allow clinicians to better understand and treat diseases like REM sleep behaviour disorder - a devastating neurodegenerative disease that in 80% of patients eventually leads to Parkinson's disease or dementia with Lewy bodies.