Molecular and functional characterization of circuits underlying social motivation in mouse models of autism

  • Awarded: 2020
  • Award Type: Pilot
  • Award #: 673021

Animals display a strong motivation to engage in social interactions and maintain social bonds. By contrast, social isolation induces a negative emotional state (loneliness) that enhances the motivation to seek social interactions. This social motivation is disrupted in autism spectrum disorder (ASD), and children with ASD display changes in the capacity to orient to social stimuli and reduced response to social reward. A better understanding of neural mechanisms underlying social motivation may provide significant insights into the basic mechanisms underlying ASD and suggest new avenues for treatment.

The laboratory of Catherine Dulac has developed a naturalistic behavioral paradigm that enables the quantification of the effect of social isolation. Preliminary data using two distinct genetic mouse models of ASD (Cntnap2 and Shank3B knockout mice), show a significant impairment in behavioral displays typically associated with isolation compared to wild-type mice. Systematic analysis of neuronal activity in the brain of wildtype mice demonstrates unique activity patterns during social isolation and social interactions. Similar experiments will be performed in Cntnap2 and Shank3B knockout mice to uncover changes in patterns of activity compared to wild type; neuronal populations displaying such changes in activity will be characterized further.

These findings will provide information about the identity and hence possible functions of the neuronal populations involved, thus enabling future investigation of causality between altered patterns of brain activity and the observed changes in social behaviors. Overall, this study should provide mechanistic insights into the nature and function of neuronal circuits associated with social motivation in both neurotypical and ASD conditions.

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