Prefrontal cortex and striatum dissociate modality and learning order in cross-modal sensorimotor learning

Sensorimotor learning is accompanied by the emergence and strengthening of sensory responses in the prefrontal cortex (PFC) and striatum. However, it remains unclear whether learning-evoked sensory responses in these structures are modality-specific, or whether they represent a more generalized signal for modality-independent but behaviorally relevant stimuli. To address this question, we performed widefield calcium imaging while mice were trained on sensorimotor tasks involving either visual or auditory stimuli, with mice first learning one modality and then switching to the other. We found that the anterior PFC (aPFC) exhibited a bilateral response to both visual and auditory stimuli after learning the respective tasks, indicating a generalized sensory representation. In contrast, the medial PFC (mPFC) showed modality-specific activity, responding only to contralateral visual stimuli after learning. Mice were able to learn sensorimotor associations for both modalities in sequence, and were only able to transfer learned behavior from visual to auditory stimuli but not the reverse. Despite differences in cross-modal learning transfer, cortical responses to learned stimuli were the same regardless of learning order. In contrast, electrophysiological recordings in the anterior striatum revealed that visually responsive regions became co-responsive to auditory stimuli only in mice trained on the visual task first. The additional auditory responses arose from distinct neurons rather than those previously responsive to visual stimuli, indicating that co-responsiveness occurred at the regional rather than single-neuron level. Together, these findings reveal that learned sensory responses in the PFC and striatum uniquely dissociate modality and learning order, suggesting a divergence in their roles during sensorimotor learning.