Basal ganglia circuits underlying repetitive behaviors in autism

  • Awarded: 2012
  • Award Type: Research
  • Award #: 240005

Repetitive behaviors are common in several neuropsychiatric disorders, including obsessive-compulsive disorders and autism spectrum disorders. Guoping Feng and his team are investigating the pathological mechanisms underlying repetitive behaviors, with the aim of understanding the neural mechanisms and genetic factors that cause or contribute to autism.

The team’s previous studies in mice show that deletion of the SAPAP3 gene, which is implicated in obsessive-compulsive disorders, leads to repetitive behaviors1. The gene’s deletion leads to defective neuronal communications in the basal ganglia, a brain region known to be involved in voluntary movement.

There are two circuits within the basal ganglia, known as the direct and indirect pathways. Feng’s group generated transgenic mice in which SAPAP3 expression can be selectively turned on or off in these two pathways. They found that selective re-expression of SAPAP3 in the direct pathway of the basal ganglia completely reverses the repetitive behavior seen in mice lacking SAPAP3. This effect is not seen in the indirect pathway, indicating that the two pathways play different roles in the pathogenesis of repetitive behavior.

Feng’s group also studied SHANK3, which interacts with SAPAP3 protein in the basal ganglia. SHANK3 mutations are strongly linked to an autism spectrum disorder called Phelan-McDermid syndrome2. The researchers found that deletion of the SHANK3 gene in mice leads to repetitive behaviors similar to those seen in mice lacking SAPAP33. Importantly, the researchers discovered similar neuronal communication defects in the basal ganglia of SHANK3 and SAPAP3 mutant mice. Together, these results provide strong evidence for a common basal ganglia circuitry mechanism underlying repetitive behavior4.



1.Welch J.M. et al. Nature 448, 894-900 (2007) PubMed
2.Durand C.M. et al. Nat. Genet. 39, 25-27 (2007) PubMed
3.Peça J. et al. Nature 472, 437-442 (2011) PubMed
4.Ting J.T. and G. Feng Curr. Opin. Neurobiol. 21, 842-848 (2011) ScienceDirect
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