Autism spectrum disorders (ASD) are characterized by difficulties in social decision-making, posing a significant challenge for individuals with ASD. To develop effective interventions and improve social functioning, it is crucial to gain a mechanistic understanding of the neural mechanisms underlying social decision-making and its impairments observed in individuals with ASD. In humans, these processes are often studied with experimental economics tasks using game theory, which have revealed alterations in neural dynamics among individuals with ASD. Nevertheless, the specific neural circuits and computations involved in these impairments remain unknown due to limited circuit-dissection tools and a lack of translatable tasks in animal models.

Herbert Wu and colleagues aim to study social decision-making alterations in ASD by developing a novel cooperative foraging paradigm in mice. Preliminary studies have shown that wildtype mice learn to cooperate, while mice with an ASD-associated mutations exhibit impaired task performance and disrupted behavioral dynamics. The prefrontal cortex (PFC), particularly the medial PFC (mPFC), is crucial in social behavior and displays different activity patterns in individuals with ASD. Wu and colleagues hypothesize that ASD risk genes disrupt social decision-making by affecting the prefrontal circuit. To test this, the team will use molecular and systems tools to investigate ASD mouse models (Adnp and Shank3) in the cooperative foraging paradigm, focusing on how ASD risk genes affect neural representations and coordinated mPFC activity between the two mice.

By applying a novel cooperative foraging paradigm, Wu and colleagues aim to elucidate neural circuit mechanisms underlying deficits in social decision-making in mouse ASD models. The research promises to uncover specific circuit disruptions and computational alterations contributing to social decision-making impairments in ASD, ultimately informing diagnosis and the development of targeted interventions.