Direct Visualisation of Abnormal Dendritic Spine Morphology in the Hippocampus of the R6/2 Transgenic Mouse Model of Huntington's Disease

Abstract

Background: Spatial learning deficits are observed in R6/2 mice, a transgenic mouse model of Huntington's Disease (HD). Spatial learning is a hippocampal-dependent process, and impairment of memory is thought to be due, at least in part, to structural changes such as loss of dendritic spines. Objective: To analyse dendritic spines in the hippocampus of R6/2 mice to determine if there are changes that correlate with the hippocampal dysfunction observed in these mice. Methods: A double transgenic cross between R6/2 mice and a reporter line (YFP-H) of mice that express yellow fluorescent protein (YFP) in a subset of their neurons was used. This allowed us to visualise dendritic spines in the brains of R6/2 mice directly. Results: Clear differences were seen in the distribution of YFP in the hippocampal formation of wild-type (WT)-YFP-H and R6/2-YFP-H mice, particularly in the CA1 region. We quantified dendritic spine density and dendritic spine length in the apical dendrites of the CA1 hippocampal neurons. A significant reduction in dendritic spine density, and a concomitant increase in dendritic spine length was observed in R6/2-YFP-H mice compared to WT-YFP-H mice. Conclusion: The R6/2-YFP-H mouse is a useful tool for directly visualising dendritic spines in the brain of a Huntington's disease mouse model. The changes we observed in dendritic spine density and length in the hippocampus might contribute to the synaptic plasticity deficits and behavioural alteration of impaired spatial learning seen in R6/2 mice.