Normal electrical properties of hippocampal neurons modelling early Huntington disease pathogenesis

Brain Res. 2007 Mar 30:1139:226-34. doi: 10.1016/j.brainres.2006.12.091. Epub 2007 Jan 9.


Huntington disease (HD) is a neurodegenerative disorder caused by an unstable and progressive expansion of a CAG trinucleotide repeat tract in the HD gene. Previous studies using truncated forms of the HD gene have shown pronounced deficits in synaptic transmission and plasticity but rather modest changes in intrinsic cellular properties, despite overt pathology. The knock-in mice carrying a 72-80 CAG repeat mutation is an accurate genetic model of early stage HD, displaying a more subtle disease phenotype. To relate full-length HD gene expression and differential polyglutamine expansion with possible pathophysiological changes in salient electrophysiological properties of neurons that may underlie early symptoms of HD, including mood and cognitive impairments, we have conducted whole-cell recordings from hippocampal area CA1 pyramidal cells in Hdh6/Q72 and Hdh4/Q80 knock-in mice. Electrophysiological characterisation of cells obtained from young adult (<4 months) HD mice harbouring an expanded CAG repeat stretch and age-matched wild type (WT) mice revealed no significant differences in any of the active or passive membrane properties investigated. Similar findings, showing a lack of significant differences in cellular electrical properties, were obtained from cells of aged (>18 months) HD mice and WT controls, despite modest levels of repeat length variability demonstrated by single cell PCR. Thus, the current study indicates a lack of overt changes in the electrical membrane properties of pyramidal cells in HD mice accurately modelling early stage HD pathology. Furthermore, together with our previous work, these findings point to a synaptic rather than cellular locus of HD-related pathology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Disease Models, Animal
  • Electrophysiology
  • Hippocampus / cytology
  • Hippocampus / physiology*
  • Huntington Disease / physiopathology*
  • Matched-Pair Analysis
  • Membrane Potentials / physiology*
  • Mice
  • Mice, Neurologic Mutants
  • Mice, Transgenic
  • Patch-Clamp Techniques
  • Pyramidal Cells / physiology*
  • Trinucleotide Repeat Expansion / physiology