Thesis

Effects of modulating pontine astrocyte activity on REM sleep in vivo

Downloadable Content

Download PDF
Creator
Rights statement
Awarding institution
  • University of Strathclyde
Date of award
  • 2024
Thesis identifier
  • T17156
Person Identifier (Local)
  • 202186625
Qualification Level
Qualification Name
Department, School or Faculty
Abstract
  • Sleep is an essential process for physical and cognitive health, and plays an important role in cognitive processes such as learning and memory. Impairments to the sleepwake cycle, including reductions in rapid eye movement (REM) sleep occur alongside cognitive deficits in many neurodegenerative diseases, such as Alzheimer’s Disease (AD). However, many aspects of sleep regulation, particularly for REM sleep remain to be fully characterised. Across the sleep-wake cycle, astrocytic intracellular Ca2+ levels fluctuate, with distinct changes occurring across different brain regions. Conflicting results have been reported regarding astrocytes in the pons, a region which is known to be involved in regulating REM sleep, with both reduced and relatively high Ca2+ signals upon REM sleep induction being reported. Thus, how pontine astrocytes contribute to REM sleep regulation remains unclear. Bridging the gap in this knowledge would benefit our understanding of REM sleep regulation, and provide valuable insight for disorders in which REM sleep is altered. In this project, we hypothesised that manipulating pontine astrocyte activity would modulate REM sleep regulation. To test this, we virally induced hM3Dq receptor expression in pontine astrocytes, under the control of a gfaABC1D promotor, and monitored electroencephalography (EEG) and electromyography (EMG) activity to classify sleep states. We found that activating pontine astrocytes causes a significant reduction in the total percent of REM sleep and the number of REM sleep episodes across six hours in a dose-dependent manner (1, 5, and 10 mg/kg clozapine-N-oxide (CNO)) compared to controls. We also show that rebound REM sleep in the hours following this effect did not occur. We next hypothesised that the reductions in REM sleep caused by chemogenetic manipulations of astrocytes would have a detrimental effect on spatial memory. We found a trend for reduced spatial memory, but not object recognition memory, in chemogenetically modified mice. Finally, we conducted a pilot study to determine if astrocytic Ca2+ levels were increased following CNO administration. We observed some state-dependent changes in v exemplar data but were not able to confirm this trend across animals due to technical limitations. Overall, our study shows that REM sleep is reduced following chemogenetic activation of pontine astrocytes. We included appropriate negative controls to validate our findings. For the first time, we show that this effect is dose dependent, does not induce rebound REM sleep, and has a tendency to impair spatial memory. Thus, in summary, our results suggest a causal role of pontine astrocytes in REM sleep induction, which is an important finding for our understanding of REM sleep regulation.
Advisor / supervisor
  • Sakata, Shuzo
Resource Type
DOI

Relations

Items

Thumbnail Title Date Uploaded Visibility Actions
file details PDF of thesis T17156 2025-06-17 Public Download
file details File 2025-06-16 Private