Corticostriatal network dysfunction in Huntington's disease: Deficits in neural processing, glutamate transport, and ascorbate release

CNS Neurosci Ther. 2018 Apr;24(4):281-291. doi: 10.1111/cns.12828. Epub 2018 Feb 21.


Aims: This review summarizes evidence for dysfunctional connectivity between cortical and striatal neurons in Huntington's disease (HD), a fatal neurodegenerative condition caused by a single gene mutation. The focus is on data derived from recording of electrophysiological signals in behaving transgenic mouse models.

Discussions: Firing patterns of individual neurons and the frequency oscillations of local field potentials indicate a disruption in corticostriatal processing driven, in large part, by interactions between cells that contain the mutant gene rather than the mutant gene alone. Dysregulation of glutamate, an excitatory amino acid released by cortical afferents, plays a key role in the breakdown of corticostriatal communication, a process modulated by ascorbate, an antioxidant vitamin found in high concentration in striatum. Up-regulation of glutamate transport by drug administration or viral-vector delivery improves ascorbate homeostasis and neurobehavioral processing in HD mice. Further analysis of electrophysiological data, including the use of sophisticated computational strategies, is required to discern how behavioral demands modulate the flow of corticostriatal information and its disruption by HD.

Conclusions: Long before massive cell loss occurs, HD impairs the mechanisms by which cortical and striatal neurons communicate. A key problem identified in transgenic animal models is dysregulation of the dynamic changes in extracellular glutamate and ascorbate. Improved understanding of how these neurochemical systems impact corticostriatal communication is necessary before an effective therapeutic strategy can emerge.

Keywords: Huntington's disease; ascorbate release; behavioral electrophysiology; corticostriatal circuit; functional connectivity; glutamate transport.

Publication types

  • Review

MeSH terms

  • Animals
  • Ascorbic Acid / metabolism*
  • Glutamic Acid / metabolism*
  • Humans
  • Huntington Disease / physiopathology*
  • Neural Pathways / physiopathology
  • Neurons / physiology*


  • Glutamic Acid
  • Ascorbic Acid