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Title: Hypothalamic control of body temperature and sleep
Author: Harding, Edward
ISNI:       0000 0004 7228 8621
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2016
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The role of sleep is not understood but it is essential for life. The sleep cycle is highly correlated to the circadian control of core temperature which, in mammals, is lower during the sleep phase. General anaesthetics induce sedation with sleep-like features, but this often comes with hypothermia. The preoptic hypothalamus seems key to the successful regulation of sleep and thermoregulation. We hypothesise a convergence of neuronal circuits that regulate sleep and temperature regulation in the preoptic area. These may also form a neuronal target for general anaesthetics. Using a pharmacogenetics technique called TetTagging it is possible to label neuronal circuits that respond to specific stimuli and then reactivate them later using a drug called clozapine N-oxide. I have used this technique to label neurons involved in the response to skin warming and used the reactivation to investigate the role of this circuit in sleep. I have also developed techniques to manipulate neuronal circuits through cooling to aid this investigation. By measuring EEG and core temperature, I found that recapitulation of activity in these warm-sensitive circuits induces strong delta oscillations, similar to those of natural sleep, followed by profound hypothermia more closely resembling the effects of general anaesthetics. A reduction in theta power was slower than the onset of delta and so may indicate an increase in sleep pressure. Following hypothermia, this state more closely resembled consolidated NREM, with REM sleep almost entirely absent. Immunohistochemistry has ruled out a GABAergic or cholinergic identity for these neurons.
Supervisor: Franks, Nicholas ; Wisden, William Sponsor: Biotechnology and Biological Sciences Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral