Neural basis for observational learning in autism mouse models

  • Awarded: 2022
  • Award Type: Pilot
  • Award #: 968348

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental condition with core characteristics that are broadly categorized as problems with social engagement that are proposed, in part, to emanate from an inability to interpret others’ intentions. This capacity to infer others’ mental states (termed theory of mind) is a critical social skill and is linked to the difficulty of children with ASD to engage in imitation behaviors which are crucial for the development of early cognitive and language skills. Observational social learning is also utilized by many animals including birds, nonhuman primates and rodents. These behaviors are thought to parallel intricate human social skills but have yet to be assessed in ASD model organisms.

Anis Contractor’s lab have preliminary data that observational learning is disrupted in a genetic mouse model of ASD (Cacna1d G407R knock-in mice). In this study, contractor and colleagues propose to test two further ASD mouse models: Shank3 (delta4-22) and 16p11.2 heterozygous mice. The team plan to assess if these mice have challenges in two parallel tests of observational learning. Moreover, they plan to use genetic and imaging tools to define the brain regions and spatiotemporal dynamics of neural activity correlated with these behaviors and determine whether these are disrupted in the mutant mice. These studies will provide a systematic analysis of the neural correlates of observational learning, a prosocial behavior, and determine whether there are shared deficits in Shank3 (delta4-22) and 16p11.2 heterozygous mice.

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