Functional interactions within striatal microcircuit in animal models of Huntington's disease

Neuroscience. 2012 Jun 1;211:165-84. doi: 10.1016/j.neuroscience.2011.06.075. Epub 2011 Jul 1.


Mutant huntingtin (mhtt) causes loss of synaptic plasticity and selective degeneration of striatal medium spiny neurons (MSNs), a core pathological feature of Huntington's disease (HD). However, projecting neurons become dysfunctional in the very early stages, long before death and this dysfunctional state may contribute to disease. Interneurons appear to be more resistant to the effects of mhtt and play important roles in supporting the activity of projecting neurons. Therefore, early modifications in the plasticity or in the pattern of cortical and striatal interneuronal activity may also be a factor in the alteration of the corticostriatal pathway in HD. While new models of HD provide information on the onset of complex behavioral changes, the mechanisms underlying alterations of the striatal microcircuit and their role in HD pathogenesis are still unclear. As a consequence, despite the development of new compounds, no adequate treatment is so far available to stop or reverse HD. Electrophysiological studies provide crucial information on neuronal dysfunction and circuit changes that underlie or precede symptoms. Here we review recent papers in which HD models have been used to study various aspects of neuronal physiology of corticostriatal pathway. We will also discuss advantages and limitations of rodent models compared to primate models and current challenges of therapies aimed at rescuing striatal function in HD.

Publication types

  • Review

MeSH terms

  • Animals
  • Cerebral Cortex / physiopathology*
  • Corpus Striatum / physiopathology*
  • Disease Models, Animal*
  • Humans
  • Huntingtin Protein
  • Huntington Disease / chemically induced
  • Huntington Disease / genetics
  • Huntington Disease / physiopathology*
  • Interneurons / physiology*
  • Models, Neurological
  • Nerve Tissue Proteins / genetics
  • Neural Pathways / physiopathology
  • Neurotoxins / toxicity
  • Synaptic Transmission / physiology


  • HTT protein, human
  • Huntingtin Protein
  • Nerve Tissue Proteins
  • Neurotoxins