Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.633193
Title: Hippocampal network function in mouse models of cognitive disease
Author: Witton, Jonathan
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2013
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Abstract:
Current evidence suggests that aberrant function in hippocampal circuits underlies cognitive impairment in Alzheimer's disease (AD) and Down syndrome (DS). Work presented in this thesis investigates novel aspects of hippocampal neurophysiology in mouse models of AD and DS. The first results chapter presents evidence for aberrant function in the dentate gyrus (DG) - CA3 network in the Tc1 mouse model of DS. Short-term synaptic plasticity was impaired in the mossy fibre pathway (MFP) in Tc1 mice, highlighting a possible impairment of information transfer between DG and CA3. Furthermore, preliminary evidence suggests possible enhancement of DG network inhibition in Tc1 mice. The second results chapter investigates synaptic transmission and plasticity in the MFP in hippocampal slices prepared from aged beta-amyloid (A~) overproducing mice. Although baseline synaptic transmission was intact, short-term and NMDA receptorindependent long-term potentiation were reduced in the MFP in - 2 year old Tg2576 mice. These results suggest that amyloid-associated neuropathology may induce deficits in information processing in the DG - CA3 network. In the third results chapter, chronically implanted tetrodes were used to investigate CA 1 network and pyramidal cell activity in the rTg4510 mouse model of tauopathy. These studies revealed a prominent decrease in the power of CA 1 network oscillations, reduced theta-gamma phase-amplitude coupling, and reduced burst firing and theta modulation of CA 1 pyramidal cells in 7 - 8 month old rTg451 0 mice. These changes in hippocampal neurophysiology may contribute to spatial memory impairment in rTg4510 mice. Finally, the fourth results chapter reports a preliminary investigation of hippocampal - prefrontal network interactions in the PSAPP mouse model of amyloidopathy during the performance of a spatial working memory task. The data suggest a possible aberrant enhancement of prefrontal - hippocampal connectivity which may contribute to spatial working memory impairment in these mice. Overall, the results presented provide multiple novel insights into hippocampal dysfunction in mouse models of AD and DS.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.633193  DOI: Not available
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