Sex-based modulation of cognitive processes could set the stage for individual differences in vulnerability to neuropsychiatric disorders. While value-based decision making processes in particular have been proposed to be influenced by sex differences, the overall correct performance in decision making tasks often show variable or minimal differences across sexes. Computational tools allow us to uncover latent variables that define different decision making approaches, even in animals with similar correct performance. Here, we quantify sex differences in mice in the latent variables underlying behavior in a classic value-based decision making task: a restless 2-armed bandit. While male and female mice had similar accuracy, they achieved this performance via different patterns of exploration. Male mice tended to make more exploratory choices overall, largely because they appeared to get “stuck” in exploration once they had started. Female mice tended to explore less, but learned more quickly during exploration. Together, these results suggest that sex exerts stronger influences on decision making during periods of learning and exploration than during stable choices. Exploration during decision making is altered in people diagnosed addictions, depression, and neurodevelopmental disabilities, pinpointing the neural mechanisms of exploration as a highly translational avenue for conferring sex-modulated vulnerability to neuropsychiatric diagnoses.

Thirty-two BL6129SF1/J mice (16 males and 16 females) were obtained from Jackson Laboratories (stock #101043). Mice arrived at the lab at 7 weeks of age, and they were housed in groups of four with ad libitum access to water while being mildly food restricted (85-95% of free feeding weight) for the experiment. Animals engaging in operant testing were housed in a 0900–2100 hours reversed light cycle to permit testing during the dark period. Before operant chamber training, animals were food restricted to 85%-90% of free feeding body weight. Operant testing occurred five days per week (Monday-Friday). All animals were cared for according to the guidelines of the National Institution of Health and the University of Minnesota.

Behavioral task. Two-armed spatial restless bandit task. Animals were trained to perform a two-armed spatial restless bandit task in the touchscreen operant chamber. Each trial, animals were presented with two identical squares on the left and right side of the screen. Nose poke to one of the target locations on the touchscreen was required to register a response. Each location is associated with some probability of reward, which changes independently over time. For every trial, there is a 10% chance that the reward probability of a given arm will increase or decrease by 10%. All the walks were generated randomly with a few criteria: 1) the overall reward probabilities of two arms are within 2% of each other, preventing one arm being overly better than the other, 2) the reward probability cannot go down to 0% or go up to 100%, 3) there are no 30 consecutive trials where the reward probabilities of both arms are lower than 20% to ensure motivation. Animals ran a simple deterministic schedule on Monday to re-adapt to operant chamber after weekends off and ran a different restless bandit task each day from Tuesday to Friday. Animals ran for 2 rounds of 4 consecutive days and within each day, animals completed either 300 trials or spent a maximum of two hours in the operant chamber. Data was recorded by the ABET II system and was exported for further analysis. All computational modeling was conducted using python.

Detailed data analyses can be found: https://www.biorxiv.org/content/10.1101/2020.12.29.424773v2