Exploring Interactions between the Sleep Homeostatic Process and Cortical Neuronal Dynamics

Lead Research Organisation: University of Oxford
Department Name: Interdisciplinary Bioscience DTP

Abstract

My DPhil project involves the use of a combination of electrophysiological recording, pharmacology and mathematical modelling to explore interactions between the sleep homeostatic process (that which increases during wake and decreases during sleep) and activity in cortical neurones in mice. The main purpose of the project is to gain additional insight into the precise origins of this process, which reflects the ultimate functions of sleep in the brain. Specifically, I use adaptations of classic models of the sleep homeostatic process, which can be measured in the slow wave (0.5-4 Hz) activity levels of locally recorded field potentials, to explore its variability across a patch of cortex and determine to what extent this can be accounted for by local variation in recent neuronal activity. I further explore how theoretically motivated measures of neuronal dynamic state, related to criticality and neuronal avalanches, vary across the sleep-wake cycle and as a function of the sleep homeostatic process. Finally, I investigate, in mice, the effects of agonists of the 5-HT2A receptor, which induce potent alterations to the quality of wakefulness, on the occurrence of sleep and on the build-up and dissipation of sleep pressure.
The project addresses the BBSRC priority area data driven biology.

Publications

10 25 50

Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011224/1 01/10/2015 31/03/2024
1810151 Studentship BB/M011224/1 01/10/2015 31/03/2020
 
Description My work has characterised in a mathematical model the link between local neuronal activity levels and changes in homeostatic sleep pressure at both the local and whole brain level. Our results suggest that the spatiotemporal integration of neural activity might be used by the brain to track time spent awake or asleep, and thereby enforce a daily sleep quota.
Recent work has explored the effects of serotonin 2A receptor agonists on sleep and sleep homeostasis. This class of drugs are interesting because of recent evidence supporting their efficacy as a treatment for a variety of mental health conditions, although the possible involvement of sleep in this effect remains unknown. We identified short-term changes in sleep-wake architecture induced by the drug, including a fragmentation of initial sleep, but no changes to the build-up of sleep pressure.
Exploitation Route My work identifying the effects of 5-HT2AR agonists on sleep is preliminary will be continued by others. This line of research is highly useful as these drugs show promising anti-depressant action, althought the fundamental mechanisms underlying this effect are unclear.
The modelling results might be useful for others who are seeking to quantify changes in sleep dynamics in the brain in response to particular, behavioural conditions, pharmacological interventions, genetic backgrounds, etc.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology