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Title: Developing a mouse preparation to study neurovascular coupling in health and ageing
Author: Shaw, Kira
ISNI:       0000 0004 6062 4931
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2016
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The aim of this research was to develop a mouse preparation suitable for studying neurovascular coupling in health, development and ageing. Neurovascular coupling is the process linking increases in neuronal activity with corresponding increases in local cerebral blood flow. Exactly how these processes are linked is still a matter of debate, although a range of cellular mechanisms, including astrocytes, pericytes, and interneurons, have been proposed to play a role. The study of neurovascular coupling is of prime importance, as haemodynamic changes are used in blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI), to make inferences about underlying neuronal responses. Further, it is thought that neurovascular coupling may be impaired in ageing, or in certain neurodegenerative diseases, e.g. Alzheimer's disease. Recent work has applied high spatiotemporal resolution, invasive techniques (e.g. two-dimensional optical imaging spectroscopy, and a multichannel electrode) to study neurovascular coupling in in vivo rodent preparations. Whilst the use of a rodent preparation allows for the detailed investigation of neurovascular responses, there are confounds associated with the effects of anaesthesia or behavioural state (i.e. active or passive) on cerebral physiology. Here, neurovascular coupling was investigated in an in vivo mouse model using an awake, head-fixed preparation or an anaesthetised preparation, in health, development and ageing. The major findings indicated that: (1) haemodynamic responses could be measured in an awake, head-fixed mouse chronically for up to 3 months; (2) locomotion profoundly altered the haemodynamic responses recorded from awake subjects; (3) a balanced, modular anaesthesia regime could be administered which resulted in comparable haemodynamic responses between awake and anaesthetised subjects; and (4) neurovascular coupling was altered in development and old age. These findings provide important insights on how behaviour, anaesthesia and ageing may affect neurovascular responses in the widely-researched mouse model.
Supervisor: Berwick, Jason ; Boorman, Luke ; Jones, Myles Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available