Sleep state-dependent functions of pontine waves

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Sleep is essential. Poor sleep is associated with various brain disorders, such as depression, dementia, and other neurodegenerative diseases as well as psychiatric disorders. Sleep can be determined by electrophysiological signatures and classified into two major sleep states: rapid eye movement (REM) sleep and non-REM (NREM) sleep. Each sleep stage is characterised by a unique set of brain waves. For example, during NREM sleep, delta waves or slow wave activity can be seen. During REM sleep, theta waves can be seen. In addition to such brain waves that appear in electroencephalography (EEG), the pons is also known to generate a prominent subsecond brain wave, called "pontine waves" or P-waves. Recently our group has established an experimental approach to monitor P-waves in a mouse model. We found that P-waves can be observed during both NREM and REM sleep and that P-waves are coupled with brain waves generated in the hippocampus. Because the hippocampus is well known to be critical for learning and memory, in this project, we will experimentally test the hypothesis that P-waves play a role in memory consolidation.To this end, we will conduct three major experiments:Firstly, we will examine if the such functional coupling between P-waves and hippocampal waves can be realized through neuronal activation across multiple brain regions which establish communications between the pons and the hippocampus. Secondly, we will determine if P-waves can activate a specific set of neurons that produce a neurotransmitter, called acetylcholine, and provide inputs to the hippocampus, and if the level of acetylcholine is increased after P-waves, and if the such increase in acetylcholine prohibits the generation of another brain wave in the hippocampus. Finally, we will determine if artificial control of P-waves can affect memory and if such effects depend on sleep stages. To achieve these goals, we will combine various state-of-the-art technologies to monitor and control neuronal activity. The outcomes of this project will shed light on the importance of sleep-related activity in the pons for not just sleep regulation, but also cognitive functions, such as memory. Ultimately, these outcomes will provide an opportunity to identify novel markers of brain disorders and develop a novel treatment for them.