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Title: Neural mechanisms of sleep and anaesthesia
Author: Steinberg, Eleonora
ISNI:       0000 0004 5920 8287
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2015
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The daily transition we take in and out of sleep is ancient and occurs in all known mammals. Ancient also is human manipulation of this transition - across cultures there have been herbal remedies to prolong wake, shorten latency to sleep and induce a state of reversible unconsciousness known as anaesthesia. While we have discovered specific brain structures necessary for maintenance of sleep and wake and protein channels targeted by anaesthetics, much still remains unknown. This study aimed to elucidate which neuronal pathways are recruited in sleep, wake and anaesthesia by studying the EEG and behaviour of genetically manipulated mice. Study of TASK-3 potassium channel knockout mice, which are less sensitive to anaesthetics, revealed increased wakefulness, resistance to stress and normal sensitivity to wake-promoting compounds. These mice also unexpectedly revealed an inability to return to normal temperature after drug-induced hypothermia. Meanwhile, study of mice in which the wake-active locus coeruleus (LC) was selectively manipulated using adeno-associated viral vectors revealed that LC suppression increases rapid-eye-movement sleep. Conversely, selective activation of the LC via designer drug receptors maintained wake but paradoxically produced behavioural arrest. Both studies reveal that the neuronal mechanisms that control sleep and anaesthesia are complex. Manipulation of crucial channels (TASK-3) and crucial regions (LC) change sensitivity to specific anaesthetics and produce distinct changes in sleep-wake that cannot be generalized to all anaesthetics or all aspects of sleep architecture. Nevertheless, these findings contribute novel insights into individual components of the ancient and complex neural circuits that orchestrate sleep, wake and anaesthesia.
Supervisor: Franks, Nicholas ; Wisden, William Sponsor: Biotechnology and Biological Sciences Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available