Article

A similar impairment in CA3 mossy fibre LTP in the R6/2 mouse model of Huntington's disease and in the complexin II knockout mouse.

Department of Anatomy, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
European Journal of Neuroscience (Impact Factor: 3.67). 11/2005; 22(7):1701-12. DOI: 10.1111/j.1460-9568.2005.04349.x
Source: PubMed

ABSTRACT Complexin II is reduced in Huntington's disease (HD) patients and in the R6/2 mouse model of HD. Mice lacking complexin II (Cplx2-/- mice) show selective cognitive deficits that reflect those seen in R6/2 mice. To determine whether or not there is a common mechanism that might underlie the cognitive deficits, long-term potentiation (LTP) was examined in the CA3 region of hippocampal slices from R6/2 mice and Cplx2-/- mice. While associational/commissural (A/C) LTP was not significantly different, mossy fibre (MF) LTP was significantly reduced in slices from R6/2 mice and Cplx2-/- mice compared with wild-type (WT) and Cplx2+/+ control mice. MF field excitatory postsynaptic potentials (fEPSPs) in response to paired stimuli were not significantly different between control mice and R6/2 or Cplx2-/- mice, suggesting that MF basal glutamate release is unaffected. Forskolin (30 microm) caused an increase in glutamate release at MF synapses in slices from R6/2 mice and from Cplx2-/- mice that was not significantly different from that seen in control mice, indicating that the capacity for increased glutamate release is not diminished. Thus, R6/2 mice and Cplx2-/- mice have a common selective impairment of MF LTP in the CA3 region. Together, these data suggest that complexin II is required for MF LTP, and that depletion of complexin II causes a selective impairment in MF LTP in the CA3 region. This impairment in MF LTP could contribute to spatial learning deficits observed in R6/2 and Cplx2-/- mice.

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    • "In R6/2 mice, polyglutamine aggregates in intranuclear and extranuclear inclusions appear early in the CA1 region, and then in neurons of the CA3 field and the dentate gyrus of the hippocampus (Morton et al., 2000). Abnormalities in hippocampal synaptic plasticity are already present by 3 weeks of age (Gibson et al., 2005), and cognitive deficits associated with hippocampal function are measurable by 4 weeks of age (Lione et al., 1999). These data, together with our results, suggest that the slow-down of theta rhythm described by us and others may be the consequence of pathophysiological changes in the hippocampus of R6/2 mice, and are likely to relate to the cognitive decline described previously in these mice. "
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