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Influence of beta-amyloid pathology on emotional learning and memory in the APPswe model of Alzheimer's disease

Lelos, Mariah Jillian ORCID: 2010. Influence of beta-amyloid pathology on emotional learning and memory in the APPswe model of Alzheimer's disease. PhD Thesis, Cardiff University.

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Previous studies have shown that both the amygdala and frontal cortex contribute to emotional and motivational processes in rodents and humans. These regions show extensive amyloid pathology in humans with Alzheimer's disease (AD) and in mouse models of AD. However, the impact of amyloid production on emotional and motivational processes in mouse models of AD has not been systematically examined. The presence of pathology within key regions linked to emotional processes led to the hypothesis that Tg2576 mice, which express a human genetic mutation associated with early onset AD, would show age-related deficits in emotional reactivity and incentive and aversive learning and memory processes. Biochemical and immunohistochemical analysis confirmed the presence of extensive amyloid pathology in cortical, amygdala and medial temporal lobe structures in Tg2576 mice. Behavioural studies established impairments in anxiety, behavioural disinhibition and fear conditioning in Tg2576 mice. In contrast, other experiments showed that appetitive instrumental and Pavlovian conditioning remained goal-directed in aged Tg2576 mice. However, context-outcome associations were insensitive to post-conditioning changes in the value of the outcome in aged but not in young Tg2576 mice. In order to gain insight into how Ap pathology influenced hippocampal-amygdala system activity during emotional learning, the final set of experiments assessed changes in the expression of the immediate early gene product c-Fos following acquisition and retrieval of fear memories. The findings from this thesis indicate that Tg2576 mice display relatively circumscribed changes in emotional reactivity and emotional memory processes that may reflect age-related alterations in amygdalo-hippocampal network interactions.

Item Type: Thesis (PhD)
Status: Unpublished
Schools: Biosciences
ISBN: 9781303191251
Date of First Compliant Deposit: 30 March 2016
Last Modified: 25 Oct 2022 08:50

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