Investigating state-dependent pontine cholinergic activity during REM sleep and P-waves in vivo

Student thesis: Doctoral Thesis

Abstract

Rapid eye movement (REM) sleep is a behavioural state during which phasic deflections in pontine LFP, known as pontine waves (P-waves), occur most prominently. Cholinergic pedunculopontine and laterodorsal tegmental nucleus (PPT/LDT) neurons have been implicated in the generation mechanisms of both REM sleep and P-waves. However, given that the PPT/LDT also contains glutamatergic and GABAergic neurons, and is surrounded by other sleep-wake regulating structures, the functional role of cholinergic PPT/LDT neurons has been difficult to discern with traditional electrophysiological, lesion and pharmacological studies.Consequently, contradictory results have been reported and a clear understanding of cell-type specific neural dynamics during REM sleep and P-waves is still lacking. Based on previous studies, it was hypothesised that cholinergic PPT/LDT neuronal activity is correlated with REM sleep initiation and P-waves. To investigate this, a fibre photometry system was designed and built to simultaneously monitor GCaMP6s fluorescence activity from cholinergic PPT/LDT neurons, EEG/EMG signals for polysomnography and pontine LFP for P-wave detection during the sleep-wake cycle in freely moving mice.Results show that cholinergic PPT/LDT activity is greatest during REM sleep, with underlying rhythmic fluctuations. P-waves were more frequent during REM sleep and for the first time, this study shows that P-waves during REM sleep coincide with larger increases in calcium transients compared to NREM sleep in mice. Additionally, peaks in GCaMP6s fluorescence peaks co-occur with P-wave during REM sleep. As sleep disturbances and cholinergic degeneration are associated with Alzheimer’s Disease (AD), a pilot study was carried out to investigate the effects of AD pathology on sleep, PPT/LDT cholinergic activity and P-waves.Preliminary results show that sleep disturbances were more profound in aging 5XFAD mice, a mouse model of AD, compared to controls. It is concluded that cholinergic PPT/LDT activity coincides with REM sleep initiation and P-waves, however functional studies are required to determine the causal relationship for both phenomena.
Date of Award18 Jun 2020
Original languageEnglish
Awarding Institution
  • University Of Strathclyde
SponsorsUniversity of Strathclyde
SupervisorShuzo Sakata (Supervisor) & Christian Wozny (Supervisor)

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