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Title: The role of complexin II in the synaptic function of the hippocampus in neurologically normal and transgenic Huntington's disease mice
Author: Gibson, H. E.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2006
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Complexin II protein expression is progressively reduced in brain tissue from Huntington’s disease (HD) patients and from the R6/2 mouse model of HD. Mice lacking complexin II (Cplx2-/-mice) show specific cognitive deficits that reflect those seen in R6/2 mice, including impairments in spatial learning. It has been suggested that abnormalities in neurotransmitter release underlie neuronal dysfunction and contribute to the symptomology associated with R6/2 mice and HD patients. The aim of this thesis was to determine whether or not there is a common synaptic mechanism that might underlie the cognitive deficits observed in Cplx2-/- and R6/2 mice. To address this aim, long-term potentiation (LTP) was examined in the hippocampus, the brain region involved in spatial learning. Hippocampal slices were prepared from two lines of mice; Cplx2-/- mice and R6/2 mice and their respective controls. Field excitatory postsynaptic potentials (fEPSPs) were recorded from the CA1 and CA3 regions. The results presented in Chapter 3 of this thesis show that, as reported previously in the literature, different forms of LTP can be distinguished in the hippocampus. In Chapter 4, the three forms of hippocampal LTP were compared between slices from Cplx2+/+ and Cplx-/-  mice. In Chapter 5, CA3 LTP was examined in slices from R6/2 mice to determine whether or not this line of mice possesses a selective deficit in CA3 mossy fibre LTP similar to that seen in slices from Cplx2-/- mice. Complexin II is required for mossy fibre LTP, but not for mossy fibre LTD, NMDAR-dependent LTP or basal neurotransmitter release at mossy fibre, associational/ commissural and CA1 synapses, since a depletion of complexin II causes a selective impairment in mossy fibre LTP in the CA3 region. Cplx2-/- mice and R6/2 mice exhibit a selective impairment of mossy fibre LTP in the CA3 region of the hippocampus that is common to both lines of mice. This impairment in mossy fibre LTP may contribute to the spatial learning deficits observed in Cplx2-/- and R6/2 mice.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available