PT - JOURNAL ARTICLE AU - Hongli Wang AU - Heather K. Ortega AU - Huriye Atilgan AU - Cayla E. Murphy AU - Alex C. Kwan TI - Pupil Correlates of Decision Variables in Mice Playing a Competitive Mixed-Strategy Game AID - 10.1523/ENEURO.0457-21.2022 DP - 2022 Mar 01 TA - eneuro PG - ENEURO.0457-21.2022 VI - 9 IP - 2 4099 - http://www.eneuro.org/content/9/2/ENEURO.0457-21.2022.short 4100 - http://www.eneuro.org/content/9/2/ENEURO.0457-21.2022.full SO - eNeuro2022 Mar 01; 9 AB - In a competitive game involving an animal and an opponent, the outcome is contingent on the choices of both players. To succeed, the animal must continually adapt to competitive pressure, or else risk being exploited and lose out on rewards. In this study, we demonstrate that head-fixed male mice can be trained to play the iterative competitive game “matching pennies” against a virtual computer opponent. We find that the animals’ performance is well described by a hybrid computational model that includes Q-learning and choice kernels. Comparing between matching pennies and a non-competitive two-armed bandit task, we show that the tasks encourage animals to operate at different regimes of reinforcement learning. To understand the involvement of neuromodulatory mechanisms, we measure fluctuations in pupil size and use multiple linear regression to relate the trial-by-trial transient pupil responses to decision-related variables. The analysis reveals that pupil responses are modulated by observable variables, including choice and outcome, as well as latent variables for value updating, but not action selection. Collectively, these results establish a paradigm for studying competitive decision-making in head-fixed mice and provide insights into the role of arousal-linked neuromodulation in the decision process.