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Thalamocortical regulation of prefrontal stability enables abstract rule generalization.

Overview

Authors: Zheng Wang1, Jingchen Liu1, Hao Liu1, Mengwei Li1, Zili Liu2, Beilin Zheng3, Yulan Zhao1, Jiping Zhang1, Liping Yu1, Jinghong Xu1
ORCID iDs: Zheng Wang, Mengwei Li, Zili Liu, Yulan Zhao, Jiping Zhang, Liping Yu, Jinghong Xu
  1. Key Laboratory of Brain Functional Genomics (Ministry of Education and Shanghai), School of Life Sciences, East China Normal University, Shanghai 200062, China
  2. Shanghai Artificial Intelligence Laboratory, Shanghai 200232, China
  3. College of Information Engineering, Hangzhou Vocational and Technical College, Hangzhou 310018, China
Institutions: East China Normal University (China); Shanghai Artificial Intelligence Laboratory (China); Hangzhou Vocational and Technical College (China)
Journal: Science advances, volume 12, issue 17, article eaec6201
Dates: received 28 September 2025; accepted 19 March 2026; published online 22 April 2026; in print April 2026
Type: Research article · Language: English
License: CC BY-NC
Identifiers: DOI 10.1126/sciadv.aec6201 · PMID 42018611 · PMCID PMC13101847 · OpenAlex W7155216701
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: mouse (organism), systems (subfield)
Methods: Spectral & time-frequency, Connectivity, Statistics, Smoothing, state filtering, decompositions, Machine learning, Single-unit activity, calcium imaging
MeSH: Generalization, Psychological*, Prefrontal Cortex*, Thalamus*, Animals, Male, Mice, Neurons (* major topic)
Topic: Neural dynamics and brain function (Cognitive Neuroscience, Neuroscience), according to OpenAlex
Funding: National Natural Science Foundation of China (31970925, 32271057, 32371046); Ministry of Science and Technology of the People's Republic of China (STI2030-Major Projects 2021ZD0202600)
Citations: not cited yet (Europe PMC); 43 references in the paper

Abstract

Our ability to generalize abstract rules to new situations is a cognitive hallmark, yet its neural basis is unclear. We identified a thalamocortical circuit essential for this process in mice. During a cross-modal rule transfer task, medial prefrontal cortex (mPFC) neurons encoded task rules across sensory modalities to enable generalization. Crucially, mediodorsal thalamus (MD) projections to mPFC were causally required: Inhibiting this pathway destabilized mPFC representations and impaired rule transfer, whereas enhancing it improved performance. Without MD input, mPFC recruited distinct populations for each task, losing cross-context stability. Direct mPFC excitation impaired generalization, underscoring the specificity of thalamic regulation. Thus, the MD stabilizes mPFC activity for flexible rule transfer—a mechanism with implications for cognitive disorders and artificial intelligence.

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

The paper's code and data availability statement is in the Data section.

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Data

Datasets cited

Data, code, and materials availability

All data and code needed to evaluate and reproduce the results in the paper are present in the paper and/or the Supplementary Materials. This study did not generate new materials. Materials used during this study can be made available upon request via the corresponding author. All data were deposited in Dryad Digital Repository, DOI: 10.5061/dryad.44j0zpcth (http://dx.doi.org/10.5061/dryad.44j0zpcth).

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 29 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 10 authors, 7 MeSH terms, 2 funders, 43 references.

Cite

This paper

Wang, Z., Liu, J., Liu, H., Li, M., Liu, Z., Zheng, B., Zhao, Y., Zhang, J., Yu, L., & Xu, J. (2026). Thalamocortical regulation of prefrontal stability enables abstract rule generalization. Science advances, 12(17), eaec6201. https://doi.org/10.1126/sciadv.aec6201

BibTeX

@article{wang2026thalamocortical,
author = {Wang, Zheng and Liu, Jingchen and Liu, Hao and Li, Mengwei and Liu, Zili and Zheng, Beilin and Zhao, Yulan and Zhang, Jiping and Yu, Liping and Xu, Jinghong},
title = {{Thalamocortical regulation of prefrontal stability enables abstract rule generalization}},
journal = {Science advances},
year = {2026},
month = apr,
volume = {12},
number = {17},
pages = {eaec6201},
publisher = {American Association for the Advancement of Science},
issn = {2375-2548},
doi = {10.1126/sciadv.aec6201},
url = {https://doi.org/10.1126/sciadv.aec6201},
pmid = {42018611},
pmcid = {PMC13101847}
}

RIS

TY - JOUR
AU - Wang, Zheng
AU - Liu, Jingchen
AU - Liu, Hao
AU - Li, Mengwei
AU - Liu, Zili
AU - Zheng, Beilin
AU - Zhao, Yulan
AU - Zhang, Jiping
AU - Yu, Liping
AU - Xu, Jinghong
TI - Thalamocortical regulation of prefrontal stability enables abstract rule generalization
T2 - Science advances
J2 - Sci Adv
PY - 2026
DA - 2026/04/22
VL - 12
IS - 17
SP - eaec6201
SN - 2375-2548
PB - American Association for the Advancement of Science
DO - 10.1126/sciadv.aec6201
UR - https://doi.org/10.1126/sciadv.aec6201
LA - en
ER -

CSL-JSON

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