Dissociating aberrant properties of recognition memory in the TC1 mouse model of Trisomy-21

Hall, Jessica H. 2016. Dissociating aberrant properties of recognition memory in the TC1 mouse model of Trisomy-21. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Down’s syndrome is a complex genetic condition arising from trisomy of chromosome 21; it is characterised by alterations in behaviour and synaptic plasticity, leading to deficits in learning and memory. The Tc1 mouse is a transchromosomic mouse model of trisomy-21 which carries a freely segregating and almost complete human chromosome 21. The main aim of this thesis was to explore recognition memory processes in the Tc1 mouse model of trisomy-21. The initial goal was to provide insight into the learning and memory changes associated with triplication of genes on human chromosome 21 in mice. The Tc1 mouse had previously been shown to display a deficit in object recognition memory following a delay of 10-min, but not following a 24-h delay. This thesis aimed to confirm and extend these findings, by testing Tc1 mice on an array of novelty based recognition tasks. This thesis also aimed to explore some of the biological systems underpinning the pattern of learning and memory changes demonstrated by the Tc1 mouse. The expression of c- fos was used as a marker of neuronal activity, allowing for the assessment of regional activity, and in addition, the expression profile of the GluR1 subunit of the AMPA receptor and the GluK1 and GluK5 subunits of the Kainate receptor were examined. Finally, this thesis investigated the impact of the administration of a novel AMPAkine, drug 9A, on the cognitive phenotype of the Tc1 mouse. The behavioural and biochemical analyses provided evidence that the Tc1 mouse model showed a selective deficit in short-term recognition memory while sparing longterm memory for the same type of information, and that a near complete copy of human chromosome 21 in Tc1 mice did not impair place recognition. In addition, c-fos expression studies provided evidence for aberrant perirhinal cortex activity in response to familiarity. Further to this, there was a significant reduction in expression of the GluR1 AMPA receptor subunit in the hippocampus, and a significant reduction of the GluK5 kainate receptor subunit expression in the perirhinal cortex. Finally, this thesis provides some preliminary evidence that a novel positive allosteric modulator, drug 9a, had a positive cognitive enhancing effect in the Tc1 mouse.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Psychology
Subjects:	B Philosophy. Psychology. Religion > BF Psychology
Date of First Compliant Deposit:	28 April 2017
Date of Acceptance:	28 April 2017
Last Modified:	24 Jan 2022 12:28
URI:	https://orca.cardiff.ac.uk/id/eprint/100194

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