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Title: Thalamocortical oscillations during sleep and general anaesthesia
Author: Baker, Rowan Harry
ISNI:       0000 0004 5989 5355
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2015
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The neuronal pathways used by general anaesthetics in order to cause loss of consciousness (LOC) are unknown. There is conflicting evidence as to whether anaesthetics exert their effects cortically or subcortically, possibly via sleep promoting pathways. Studies investigating the mechanisms underlying both natural sleep and anaesthetic-induced LOC have converged on the thalamus and neocortex, with their respective roles in instigating LOC being unclear. In this thesis, local field potentials were recorded from multiple thalamic and cortical nuclei in rats during transitions into natural sleep and anaesthetic-induced LOC using propofol and dexmedetomidine. Morlet wavelet analysis was used to visualise the time varying power spectra with high temporal resolution. Whilst anaesthetic specific changes occurred, reductions in frequency and increases in power within the 10-64Hz range of oscillations were observed occurring at, or immediately preceding, transitions into natural sleep and anaesthetic-induced LOC. These changes occurred within the central medial thalamus (CMT), a higher-order thalamic nucleus, prior to both the neocortex and a primary thalamic nucleus during transitions into natural sleep and propofol-induced LOC. For dexmedetomidine-induced LOC, these changes occurred simultaneously in all nuclei. However, following dexmedetomidine administration, a delta (1-4Hz) oscillation was induced. This oscillation reduced in frequency abruptly at the LOC point, accompanied by a sudden phase change between the CMT and all other nuclei. These results are in agreement with natural sleep and anaesthetic-induced LOC being initiated subcortically, with the CMT acting as a key mediator. Additionally, phase and spectral similarities between dexmedetomidine anaesthesia and natural sleep are consistent with dexmedetomidine utilising sleep pathways, whilst propofol only exhibits sleep-like characteristics during the recovery phase. Finally, a prototype device developed in-house capable of wirelessly transmitting six electrophysiological signals for 25 hours from rats is characterised. Further development for recording from unrestrained mice is outlined.
Supervisor: Franks, Nick Sponsor: National Institute of Academic Anaesthesia ; Royal College of Anaesthetists
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral