Learning to learn: Single session acquisition of new rules by freely-moving mice

Learning from examples and adapting to new rules are fundamental attributes of human cognition. However, it is unclear what conditions allow for fast and successful learning. To determine how rapidly freely-moving mice can learn a new rule, we designed a fully automated two-alternative forced choice visual discrimination paradigm in which the rules governing the task can change between sessions. We find that animals can learn a new rule during the very first block of trials. The propensity for single session learning improves over time and can be accurately predicted based on animal experience and rule difficulty. When conditions for generalization from a previous rule are more favorable, mice perform single session learning with higher success rates. Units recorded from hippocampal region CA1 during a previously-learned visual rule exhibit task-related place fields and state-dependent modulation. A mouse trained on visual rules can learn an intra-cortical rule, generated by direct activation of hippocampal CA1 pyramidal cells. Thus, after establishing procedural learning of a paradigm, mice continue to perform and improve at associative operant learning of new rules.