Thesis
Investigating state-dependent pontine cholinergic activity during REM sleep and P-waves in vivo
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- Awarding institution
- University of Strathclyde
- Date of award
- 2020
- Thesis identifier
- T15643
- Person Identifier (Local)
- 201665424
- Qualification Level
- Qualification Name
- Department, School or Faculty
- 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.
- Advisor / supervisor
- Sakata, Shuzo
- Resource Type
- DOI
- Date Created
- 2020
- Former identifier
- 9912892786502996
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