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Title Investigating state-dependent pontine cholinergic activity during REM sleep and P-waves in vivo / Amisha Patel.
Name Patel, Amisha. .
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.
Abstract 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.
Abstract 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.
Abstract 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.
Publication date 2020.
Name Sakata, Shuzo, degree supervisor.
Name University of Strathclyde. Strathclyde Institute of Pharmacy and Biomedical Sciences.
Thesis note Thesis Ph. D. University of Strathclyde 2020 T15643
System Number 000006059

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