Sleep state-dependent functions of pontine waves
Lead Research Organisation:
University of Strathclyde
Department Name: Inst of Pharmacy and Biomedical Sci
Abstract
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.
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.
Technical Summary
Ponto-geniculo-occipital (PGO) or Pontine waves (P-waves) have long been recognised as a hallmark of REM sleep. However, their function remains elusive.
Recently we have reported that P-waves can be observed in both REM and NREM sleep in mice, and P-waves functionally couple with hippocampal oscillations depending on sleep states: P-waves are coupled with theta oscillations during REM sleep whereas hippocampal sharp wave-ripples (SWRs) coupled with P-waves are short-lived during NREM sleep, suggesting opposing roles of P-waves in memory consolidation depending on sleep states.
In this proposal, we will test the hypothesis that P-waves are part of brain-wide coordinated activity across sleep states and that P-waves play roles in memory consolidation by functionally coupling with hippocampal oscillations in a sleep state-dependent fashion.
To this end, we propose three Work Packages (WPs).
In WP1, by utilising Neuropixels probes, we will monitor neural ensembles across brain regions and sleep-wake cycles along with P-wave monitoring. Then, we will examine if the state-dependent coupling between P-waves and hippocampal oscillations can be realised through activations of distributed brain regions.
In WP2, by performing fibre photometry and electrophysiology, we will identify a mechanism by which SWRs coupled with P-waves can be short-lived. More specifically, we will examine if P-waves can activate medial septal cholinergic neurons and increase cholinergic tone in the hippocampal CA1, leading to the suppression of SWRs.
In WP3, by combining optogenetic and behavioural approaches, we will examine if mesopontine cholinergic neurons that project to the septum play opposing roles in memory consolidation depending on sleep states.
The outcomes will provide novel insight into how P-waves can functionally interact with hippocampal oscillations across sleep states and how P-waves can contribute to systems memory consolidation.
Recently we have reported that P-waves can be observed in both REM and NREM sleep in mice, and P-waves functionally couple with hippocampal oscillations depending on sleep states: P-waves are coupled with theta oscillations during REM sleep whereas hippocampal sharp wave-ripples (SWRs) coupled with P-waves are short-lived during NREM sleep, suggesting opposing roles of P-waves in memory consolidation depending on sleep states.
In this proposal, we will test the hypothesis that P-waves are part of brain-wide coordinated activity across sleep states and that P-waves play roles in memory consolidation by functionally coupling with hippocampal oscillations in a sleep state-dependent fashion.
To this end, we propose three Work Packages (WPs).
In WP1, by utilising Neuropixels probes, we will monitor neural ensembles across brain regions and sleep-wake cycles along with P-wave monitoring. Then, we will examine if the state-dependent coupling between P-waves and hippocampal oscillations can be realised through activations of distributed brain regions.
In WP2, by performing fibre photometry and electrophysiology, we will identify a mechanism by which SWRs coupled with P-waves can be short-lived. More specifically, we will examine if P-waves can activate medial septal cholinergic neurons and increase cholinergic tone in the hippocampal CA1, leading to the suppression of SWRs.
In WP3, by combining optogenetic and behavioural approaches, we will examine if mesopontine cholinergic neurons that project to the septum play opposing roles in memory consolidation depending on sleep states.
The outcomes will provide novel insight into how P-waves can functionally interact with hippocampal oscillations across sleep states and how P-waves can contribute to systems memory consolidation.
