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Title: A window on the ageing brain : imaging synapses and their dynamics in vivo
Author: Grillo, Federico William
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2013
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The ageing process has an enormous impact on the human body and it represents a major risk factor for a number of diseases. Ageing is also associated with a progressive cognitive decline mainly involving the memory domain. Up to date many studies have investigated the structural and functional changes that occur in the ageing brain. Rather than neuronal loss, it is now widely accepted that synaptic impairments underlie the decreased cognitive performance. Such studies point to reduced synaptic density and plasticity, in specific brain regions, during ageing. However, most studies so far made use of either post-mortem or ex vivo preparations. Thus, the key question addressed in this thesis is to what extent synaptic elements are dynamic in the intact aged brain. A combination of in vivo two-photon imaging, correlated two-photon-electron microscopy and novel computational tools was used to study synaptic boutons in the aged mouse somatosensory cortex. Unexpectedly, circuit-specific increased rates of bouton formation, elimination, and destabilization were found. Age related increased dynamics greatly affected large (i.e., strong) boutons, thought to encode long-term memory, as opposed to smaller ones. The rigorous measurement of the size and location of axonal boutons, achieved for the first time in vivo, showed that while the average density and size of boutons was not affected by ageing, bouton size changes were greater in the aged animals. Such increased size fluctuations were again confined to larger, persistent boutons., Long-term memory impairment, as assessed in a novel behavioural task, was therefore associated with increased, rather than decreased, synaptic destabilization and dynamics, suggesting the existence of a novel mechanism underlying age related cognitive decline.
Supervisor: De Paola, Vincenzo Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available