Learning to link sensory information to motor actions requires coordinated activity across the cerebral cortex, but how different cortical layers contribute to learning remains unclear. Here we show that learning engages distinct, layer-specific activity patterns across the cortex of male mice during acquisition of a whisker-based go/no-go task. Using wide-field calcium imaging of either layer 2/3 or layer 5 neurons across 25 cortical areas, we found that learning produced markedly different, and sometimes opposing, changes in activity between layers.
Layer 5 exhibited widespread suppression before sensory input and enhanced activity in frontal cortex during sensorimotor transformation, whereas layer 2/3 showed learning-related enhancements in higher-order sensory areas during sensation. In contrast, both layers displayed similar learning-related enhancement in barrel cortex during whisker touch. These findings reveal complementary roles of superficial and deep cortical layers during learning and demonstrate that layer-specific cortical dynamics are a fundamental feature of sensorimotor learning.
We would like to thank Malak Abumadi and Dr. Odeya Marmor for their help with genotyping and mouse maintenance, Fritjof Helmchen and Philipp Bethge for their help with the transgenic mouse lines, and Renana Terner-Rothkoff for careful proofreading of the manuscript. This work is funded by the Einstein Foundation Research Grants (A-2021-644 and BJ-2024-850; A.G and M.E.L). the The European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (MESO-AG, 101040378; A.G.).
European Union's Horizon 2020 research and innovation program and Euratom research and training program 20142018 (No. 670118 to MEL); Deutsche Forschungsgemeinschaft (Exc 257 NeuroCure, Grant No. LA, Project number 327654276 SFB1315) Department of Medical Neurobiology, Faculty of Medicine, The Institute for Medical Research Israel-Canada (IMRIC), The Hebrew University of Jerusalem, Jerusalem, Israel Institute for Biology, Humboldt University of Berlin, Berlin, Germany Robert N. Larkum The authors declare no competing interests Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. Pollak, Y.E., Sachdev, R.N.S., Larkum, M.E. et al.
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