Subthalamic nucleus pathology contributes to repetitive behavior expression and is reversed by environmental enrichment

Genes Brain Behav. 2018 Nov;17(8):e12468. doi: 10.1111/gbb.12468. Epub 2018 Mar 15.


Repetitive motor behaviors are common in neurodevelopmental, psychiatric and neurological disorders. Despite their prevalence in certain clinical populations, our understanding of the neurobiological cause of repetitive behavior is lacking. Likewise, not knowing the pathophysiology has precluded efforts to find effective drug treatments. Our comparisons between mouse strains that differ in their expression of repetitive behavior showed an important role of the subthalamic nucleus (STN). In mice with high rates of repetitive behavior, we found significant differences in dendritic spine density, gene expression and neuronal activation in the STN. Taken together, these data show a hypoglutamatergic state. Furthermore, by using environmental enrichment to reduce repetitive behavior, we found evidence of increased glutamatergic tone in the STN with our measures of spine density and gene expression. These results suggest the STN is a major contributor to repetitive behavior expression and highlight the potential of drugs that increase STN function to reduce repetitive behavior in clinical populations.

Keywords: C58 mice; basal ganglia; environmental enrichment; repetitive behavior; subthalamic nucleus.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Basal Ganglia / physiology
  • Behavior, Animal / physiology
  • Dendritic Spines / pathology
  • Disease Models, Animal
  • Excitatory Amino Acid Agents / metabolism
  • Female
  • Gene Expression Regulation / genetics
  • Gene-Environment Interaction
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Neural Pathways
  • Neurons / physiology
  • Stereotyped Behavior / physiology
  • Stereotypic Movement Disorder / pathology*
  • Subthalamic Nucleus / pathology*


  • Excitatory Amino Acid Agents