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bioRxiv · 10.1101/2025.09.24.678380

Cooperative behavior guided by peer coordination is impaired in a Fragile-X rat model of autism

Shukla, A.·Rivera, E. L.·Bladon, J. H.·Jadhav, S. P.
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Abstract

Cooperative behavior, the ability of individuals to coordinate their actions toward shared goals, is fundamental to survival and social success across species. However, the mechanisms supporting cooperation and how their disruption leads to social deficits in neurodevelopmental disorders such as autism spectrum disorder (ASD), remain poorly understood. To address these questions, we developed a novel cooperation task in paired spatial mazes under deterministic (100%) and probabilistic (50%) reward contingencies, utilizing dyads of littermate wild-type (WT) and Fmr1 knockout (Fmr1) rats, a model of Fragile X syndrome. Both WT and Fmr1 rat pairs exhibited dynamic turn-taking with mixed leader-follower behavior for cooperation; however, WT pairs achieved significantly greater cooperation success than Fmr1 pairs. WT and Fmr1 pairs both successfully utilized a simple follower-tracking-leader reactive strategy, dependent on partner-directed visual attention, resulting in slower asynchronous transitions, with Fmr1 pairs more reliant on this strategy. WT rat pairs in addition exhibited a more efficient, flexible predictive cooperation strategy, dependent on coordination of optimal transition patterns between rat pairs and recent partner choice history, resulting in faster synchronous transitions. Fmr1 rats were unable to show adaptation to the probabilistic reward condition by employing this more efficient social reciprocity strategy of higher complexity, leading to deficits in cooperative behavior. These findings reveal key behavioral strategies of varying complexity for cooperation, reveal the specific disruption of complex social reciprocity strategies in a rat ASD model, and provide a foundation for investigation of social interactions and underlying neural mechanisms in cooperative decision-making with relevance to neurodevelopmental disorders.

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Shukla, A., Rivera, E. L., Bladon, J. H., Jadhav, S. P.. 2025-09-25. Cooperative behavior guided by peer coordination is impaired in a Fragile-X rat model of autism. https://doi.org/10.1101/2025.09.24.678380

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