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Title: Characterisation of visuospatial memory in the Tg2576 model of Alzheimer's disease
Author: Hale, Gemma
ISNI:       0000 0004 2749 9497
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2007
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Previous behavioural characterization of the Tg2576 mouse has been limited to reference memory tasks in water or T/Y mazes. This thesis aimed to specify the underlying features of visuospatial memory in this model of Alzheimer's disease. Chapter 2 presents a series of experiments that are consistent with the hypothesis that aged Tg2576 animals are impaired in forming allocentric representations of the environment. Experiments 1 and 2 demonstrated that aged transgenic mice were able to acquire a simple room discrimination and contextual conditional left-right discrimination in a T-maze. Experiment 3 showed that aged transgenic mice were able to learn a response strategy in a reference memory task in the plus maze. Tg2576 mice were however significantly impaired in the acquisition of the place version of the plus maze task and T-maze forced-choice alternation (Experiment 2 a). Using a spontaneous object recognition paradigm, Experiment 4 revealed that adult mutant mice were able to discriminate between familiar and novel objects with delays of up-to 24 hours and were also able to discriminate the relative familiarity of two objects. However, Tg2576 mice failed to investigate objects that had changed their relative spatial positions. Furthermore, Experiment 5, using an episodic-like memory task, demonstrated that Tg2576 mice were unable to integrate information concerning the temporal properties and spatial location of objects. This inability reflected a primary deficit in processing or memory for the spatial location of objects. Chapter 4 examined the nature of the spatial representations that were impaired by the APPswe mutation in versions of a spontaneous object recognition paradigm. Experiment 6 evaluated Tg2576 mouse habituation. Experiment 8 demonstrated that Tg2576 performance was not facilitated by the presence of an intra maze cue. Experiments 7 and 9 revealed that Tg2576 mice were sensitive to changes in the spatial organisation of the objects when the objects were moved to locations previously unoccupied during the sample stage. This pattern of results suggests that Tg2576 mice manifest a specific deficit in the formation of object-location associations akin to the impairment observed in Alzheimer patients (e.g., Swainson et al.,2001).
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available