Offline generative network reconfiguration guides insight-like accelerated learning by assimilation into schema in rats

Complex cross-modal de-novo associative learning generally requires numerous encoding exposures, but acquisition of an underlying mental schema of associative abstract rules enables insight-like accelerated new learning. Reports indicate that post-encoding sleep/rest offline epochs play an active role in insight learning, but the supporting neuronal ensemble mechanisms remained elusive. We developed a complex cross-modal learning task where six cue-place paired-associations (PAs) learned by male rats over weeks created a mental schema that enabled rapid within-day acquisition of 3-6 novel PAs.

Simultaneous electrophysiological recording of hippocampus (HPC)-medial prefrontal (mPFC) ensembles across exploration-rest-sleep states indicated that accelerated learning of new PAs combined inferential activation of HPC map-based cue-place abstract associations and offline generative network reconfiguration in coordination with mPFC generalized outcome coding. HPC network reconfiguration during post-encoding sleep/rest predicted insight-like accelerated learning of 3-6 new PAs that consolidated and transferred rapidly via ripple-coordinated cell-assembly co-activation to mPFC. HPC ripple disruption during post-encoding sleep/rest prevented schema-based accelerated learning.

Our findings reveal that map-based associative inference via offline predictive HPC-mPFC generative network reconfiguration supports insight-like accelerated learning by assimilation into schema and systems consolidation. Ocampo for help with task design validation and behavioral rat training protocol, and all members of the Dragoi lab for helpful discussions. G.D. discloses support for the research of this work from NIH grants R01NS104917, R01MH121372, and R35NS132342.

Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA Department of Neuroscience and Wu Tsai Institute, Yale School of Medicine, New Haven, CT, USA 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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Bhattarai, B., Dragoi, G. Offline generative network reconfiguration guides insight-like accelerated learning by assimilation into schema in rats. Nat Commun (2026). https://doi.org/10.1038/s41467-026-77318-1 DOI: https://doi.org/10.1038/s41467-026-77318-1