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Early-Stage Corticostriatal Hyperactivity Impairs Cognitive Flexibility Alongside Striatal Cholinergic Dysfunction in an Alzheimer's Disease Model.

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Paper

Loaded from Europe PMC by your browser, not stored by OSCR: doi.org · Europe PMC

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The authors' code

MATLAB · 21 lines · 605 B · no license

  2. temp = DF_F(area(1):area(2),:);
  3. lis = zeros(size(temp));
  4. AUCs = zeros(1,size(temp,2));
  5. MAXs = zeros(1,size(temp,2));
  6. fwht = zeros(1,size(temp,2));
  7. for i = 1:size(temp,2)
  8. lis(:,i) = BaselineCorrection(temp(:,i));
  9. tempp = lis(cent-area(1)+1:area(2)-area(1),i).*msksub(cent-area(1)+1:area(2)-area(1));
  10. figure
  11. plot(tempp)
  12. AUCs(i) = sum(tempp(tempp>0));
  13. MAXs(i) = max(tempp);
  14. fwht(i) = FWHT(tempp);
  15. end
  17. fwht = fwht*t(2);
  19. AUCms = [mean(AUCs),std(AUCs)/length(AUCs)];
  20. MAXms = [mean(MAXs),std(MAXs)/length(MAXs)];
  21. fwhtms = [mean(fwht),std(fwht)/length(fwht)];

AUC_Max_.m at commit 70f3a7b, no license · at the source

Overview

Authors: Yufei Huang1,2, Xueyi Xie1, Zhenbo Huang1, Ruifeng Chen1,3, Himanshu Gangal1,2, Xuehua Wang1, Karienn A. de Souza1,2, Julia Hunter1, Xin Wu1, Doodipala Samba Reddy1,2,3, Jeannie Chin4, Jun Wang1,2,3
ORCID iDs: Yufei Huang, Xueyi Xie, Karienn A. de Souza, Xin Wu, Doodipala Samba Reddy, Jun Wang
  1. Department of Neuroscience and Experimental Therapeutics, Naresh K. Vashisht College of Medicine, Texas A&M University Health Science Center,Bryan, TX USA
  2. Institute for Neuroscience, Texas A&M University,College Station, TX USA
  3. Interdisciplinary Faculty of Toxicology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University,College Station, TX USA
  4. Department of Neuroscience, Baylor College of Medicine,Houston, TX USA
Institutions: Texas A&M University (United States); Baylor College of Medicine (United States)
Journal: Nature communications, volume 17, issue 1, article 8226
Dates: received 7 October 2025; accepted 12 June 2026; published online 26 June 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s41467-026-74817-z · PMID 42362551 · PMCID PMC13462761 · OpenAlex W7166123322
Open access: gold, a free copy (OpenAlex)
Status: code verified
Categories: human (organism), mouse (organism), Alzheimer's / dementia (population)
Methods: Spectral & time-frequency, Statistics, Evoked potentials, fMRI & imaging, Single-unit activity, calcium imaging, Smoothing, state filtering, decompositions
Keywords: Neural circuits, Alzheimer's disease
MeSH: Alzheimer Disease*, Cognitive Flexibility*, Corpus Striatum*, Prefrontal Cortex*, Acetylcholine, Animals, Cholinergic Neurons, Cognition, Disease Models, Animal, Humans, Male, Medium Spiny Neurons, Mice, Mice, Transgenic, Reversal Learning, Synaptic Transmission (* major topic)
Topic: Memory and Neural Mechanisms (Cognitive Neuroscience, Neuroscience), according to OpenAlex
Funding: National Institute on Alcohol Abuse and Alcoholism (R01AA027768, U01AA025932)
Citations: cited by 2 papers (Europe PMC); 104 references in the paper

Abstract

Cognitive flexibility declines early in Alzheimer’s disease, yet the underlying circuit mechanisms remain unknown. Here, we report that young 5xFAD mice exhibit deficits in instrumental reversal learning prior to spatial memory impairment. This behavioral inflexibility is associated with abnormal neuronal reactivation in the medial prefrontal cortex and dorsomedial striatum. Electrophysiological recordings reveal that medial prefrontal cortex neurons are hyperexcitable and receive increased excitatory input. Furthermore, glutamatergic transmission from the medial prefrontal cortex to striatal direct-pathway medium spiny neurons is enhanced and coincides with strengthened inhibitory transmission onto striatal cholinergic interneurons, reduced spontaneous firing, and diminished striatal acetylcholine release. Critically, sustained chemogenetic inhibition of this corticostriatal circuit attenuates cortical amyloid accumulation, reduces glutamatergic transmission, and increases acetylcholine levels. This also rescues reversal learning deficits in 5xFAD mice. Here, we show that pathological corticostriatal hyperactivity contributes to early cognitive inflexibility in a mouse model of Alzheimer’s disease.

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

Repository

Its files are read in the Code ↔ Paper reader above.

chen-ruifeng/ex-vivo-confocal

License: none: the authors keep all their rights
State: the link answers, verified on 27 September 2026
Evidence: files inventoried
Commit: 70f3a7bceab50a04905c745e61ea4c6b939b6b62, 5 February 2024
Languages: MATLAB (28)
Size: 29 files, 28 scripts
Software Heritage: not archived
Found in: “Code availability”
Not found: README, license file, CITATION.cff, environment file, tests, continuous integration, documentation
Tools: Signal Processing Toolbox (7 files), Image Processing Toolbox (1 file)
Availability: 1 check, the latest on 27 September 2026: the link answers
  • 27 September 2026: the link answers
28 files
At the source: github.com/chen-ruifeng/ex-vivo-confocal

Code availability

Custom MATLAB analysis code used to analyze live confocal imaging data is available at GitHub: (https://github.com/chen-ruifeng/ex-vivo-confocal).

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

Tracing map

Proposed by the machine: these links were found in the paper and verified at the source, without human review. The map will receive a Zenodo DOI once one of the paper's authors has validated it with their ORCID.

What the map holds:

  • 1 repository of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
  • 28 scripts, each with its path and the digest of its content;
  • no match between paragraphs and code yet;
  • neither the text of the paper nor the code itself.

Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.

Data

No dataset and no data link were found in the paper.

Data availability

The source data generated in this study are provided in the Source Data file. This Excel file contains multiple worksheets, including the numerical data used to generate Figs. 1–7 and Supplementary Fig. 1–15, together with associated statistical information. No restricted-access datasets were used in this study. Source data are provided with this paper.

Reproduced under the paper's license (CC BY), 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, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 12 authors, 2 keywords, 16 MeSH terms, 1 funder, 103 references.

Cite

This paper

Huang, Y., Xie, X., Huang, Z., Chen, R., Gangal, H., Wang, X., de Souza, K. A., Hunter, J., Wu, X., Reddy, D. S., Chin, J., & Wang, J. (2026). Early-Stage Corticostriatal Hyperactivity Impairs Cognitive Flexibility Alongside Striatal Cholinergic Dysfunction in an Alzheimer's Disease Model. Nature communications, 17(1), 8226. https://doi.org/10.1038/s41467-026-74817-z

BibTeX

@article{huang2026early,
author = {Huang, Yufei and Xie, Xueyi and Huang, Zhenbo and Chen, Ruifeng and Gangal, Himanshu and Wang, Xuehua and de Souza, Karienn A. and Hunter, Julia and Wu, Xin and Reddy, Doodipala Samba and Chin, Jeannie and Wang, Jun},
title = {{Early-Stage Corticostriatal Hyperactivity Impairs Cognitive Flexibility Alongside Striatal Cholinergic Dysfunction in an Alzheimer's Disease Model}},
journal = {Nature communications},
year = {2026},
month = jun,
volume = {17},
number = {1},
pages = {8226},
publisher = {Nature Publishing Group},
issn = {2041-1723},
doi = {10.1038/s41467-026-74817-z},
url = {https://doi.org/10.1038/s41467-026-74817-z},
pmid = {42362551},
pmcid = {PMC13462761}
}

RIS

TY - JOUR
AU - Huang, Yufei
AU - Xie, Xueyi
AU - Huang, Zhenbo
AU - Chen, Ruifeng
AU - Gangal, Himanshu
AU - Wang, Xuehua
AU - de Souza, Karienn A.
AU - Hunter, Julia
AU - Wu, Xin
AU - Reddy, Doodipala Samba
AU - Chin, Jeannie
AU - Wang, Jun
TI - Early-Stage Corticostriatal Hyperactivity Impairs Cognitive Flexibility Alongside Striatal Cholinergic Dysfunction in an Alzheimer's Disease Model
T2 - Nature communications
J2 - Nat Commun
PY - 2026
DA - 2026/06/26
VL - 17
IS - 1
SP - 8226
SN - 2041-1723
PB - Nature Publishing Group
DO - 10.1038/s41467-026-74817-z
UR - https://doi.org/10.1038/s41467-026-74817-z
LA - en
ER -

CSL-JSON

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"id": "10.1038/s41467-026-74817-z",
"type": "article-journal",
"title": "Early-Stage Corticostriatal Hyperactivity Impairs Cognitive Flexibility Alongside Striatal Cholinergic Dysfunction in an Alzheimer's Disease Model",
"container-title": "Nature communications",
"author": [
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{
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"given": "Xuehua"
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"given": "Karienn A."
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