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

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 revealed an important role of the subthalamic nucleus. In mice with high rates of repetitive behavior, we found significant differences in dendritic spine density, gene expression, and neuronal activation in the subthalamic nucleus. Taken together, these data demonstrate a hypoglutamatergic state. Furthermore, by using environmental enrichment to reduce repetitive behavior, we found evidence of increased glutamatergic tone in the subthalamic nucleus with our measures of spine density and gene expression. These results suggest the subthalamic nucleus is a major contributor to repetitive behavior expression and highlight the potential of drugs that increase subthalamic nucleus function to reduce repetitive behavior in clinical populations.
Source: Genes, Brain and Behavior - Category: Genetics & Stem Cells Authors: Tags: ORIGINAL ARTICLE Source Type: research