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

Sensorimotor learning is accompanied by the emergence of sensory responses in the prefrontal cortex (PFC) and striatum. However, it remains unclear whether these learning-evoked sensory regions are modality-specific, or whether they represent a more generalized signal for behaviorally relevant stimuli. We addressed this question by recording activity in the cortex and striatum of mice during training on visual and auditory sensorimotor tasks.

We found that the anterior PFC developed context-dependent responses to both stimulus modalities after learning, while the medial PFC developed context-independent visual responses. Mice were able to transfer learned behavior from visual to auditory stimuli, but not the reverse. The training order of modalities did not affect responses in the PFC, while transferring from visual to auditory modalities drove auditory responses in a visually responsive region of the striatum.

These findings reveal that learned sensory responses in the PFC and striatum uniquely dissociate modality and learning order. We thank Yuliia Shevchuk for collecting part of the Neuropixels data, and Randy Bruno, Haron Avgana and Peter Gorman for proofreading the manuscript and providing valuable comments and suggestions. This work was supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (224156/Z/21/Z) to A.J.P.

Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, UK The authors declare no competing interests. Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.

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Prefrontal cortex and striatum dissociate modality and learning order in cross-modal sensorimotor learning in mice. Nat Commun (2026). https://doi.org/10.1038/s41467-026-78921-y DOI: https://doi.org/10.1038/s41467-026-78921-y