OSCR

Hcn1-dependent engram neurons in the PVN encode gastric inflammatory sensitization.

Overview

Authors: E Liu1, Xijia Xin1, Mengdong Shi1, Weikai Han1, Qingyu Ren1, Yaqi Tang1, Yanan Yue1, Chenyu Zhang1, Zhanpeng Gao1, Qingwei Yue1, Jinhao Sun1
ORCID iDs: E Liu, Qingyu Ren, Jinhao Sun
  1. Department of Anatomy and Neurobiology, Shandong University School of Basic Medicine, Jinan, Shandong, China
Institutions: Shandong University (China)
Journal: Science advances, volume 12, issue 20, article eaeb6961
Dates: received 23 August 2025; accepted 8 April 2026; published online 15 May 2026; in print May 2026
Type: Research article · Language: English
License: CC BY-NC
Identifiers: DOI 10.1126/sciadv.aeb6961 · PMID 42139357 · PMCID PMC13178568 · OpenAlex W7161263718
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: genetics / omics (modality), mouse (organism), cellular / molecular (subfield)
Methods: Spectral & time-frequency, Statistics, Smoothing, state filtering, decompositions, Evoked potentials, Single-unit activity, calcium imaging
MeSH: Gastritis*, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels*, Neurons*, Paraventricular Hypothalamic Nucleus*, Potassium Channels*, Animals, Inflammation, Male, Mice (* major topic)
Journal subjects: Neuroscience
Topic: Gastrointestinal motility and disorders (Gastroenterology, Medicine), according to OpenAlex
Funding: National Natural Science Foundation of China (82401755, U2202211, 82471517); Natural Science Foundation of Shandong Province (ZR2024QH204); Postdoctoral Fellowship Program of CPSF (GZC20240932); China Postdoctoral Science Foundation General Funding Program (2025M772673)
Citations: not cited yet (Europe PMC); 46 references in the paper

Abstract

The brain encodes peripheral inflammatory signals, but the regulatory mechanism by which the brain controls gastric inflammation remains unclear. This study reveals a circuit through which Fos-positive neurons in the paraventricular nucleus of the hypothalamus (PVN) regulate gastritis via a PVN–dorsal motor nucleus of the vagus–stomach neural circuit and the hypothalamic-pituitary-adrenal (HPA) axis. Using activity-dependent genetic labeling, chemogenetics, and optogenetics, we demonstrate that FosPVN neurons are essential for gastritis progression and can be activated by stress to drive chronic inflammation. Single-nucleus RNA sequencing (snRNA-seq) revealed up-regulation of hyperpolarization-activated cyclic nucleotide–gated channel 1 (Hcn1) in FosPVN neurons during gastritis. Inhibiting Hcn1 reduced neuronal excitability and ameliorated gastric pathology. Crucially, repeated activation of FosPVN neurons forms a specific “inflammatory sensitization,” leading to the persistence of disease, whereas stress can exacerbate gastric inflammation through these FosPVN neurons. Our findings elucidate the central neural mechanisms encoding gastric inflammation and identify Hcn1 as a potential therapeutic target for neuromodulatory treatment of chronic inflammatory diseases.

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

Code

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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. The sequencing data have been uploaded to the GEO database (record GSE296274, https://ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE296274; record GSE296273, https://ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE296273).

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, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 11 authors, 9 MeSH terms, 4 funders, 46 references.

Cite

This paper

Liu, E., Xin, X., Shi, M., Han, W., Ren, Q., Tang, Y., Yue, Y., Zhang, C., Gao, Z., Yue, Q., & Sun, J. (2026). Hcn1-dependent engram neurons in the PVN encode gastric inflammatory sensitization. Science advances, 12(20), eaeb6961. https://doi.org/10.1126/sciadv.aeb6961

BibTeX

@article{liu2026hcn1,
author = {Liu, E and Xin, Xijia and Shi, Mengdong and Han, Weikai and Ren, Qingyu and Tang, Yaqi and Yue, Yanan and Zhang, Chenyu and Gao, Zhanpeng and Yue, Qingwei and Sun, Jinhao},
title = {{Hcn1-dependent engram neurons in the PVN encode gastric inflammatory sensitization}},
journal = {Science advances},
year = {2026},
month = may,
volume = {12},
number = {20},
pages = {eaeb6961},
publisher = {American Association for the Advancement of Science},
issn = {2375-2548},
doi = {10.1126/sciadv.aeb6961},
url = {https://doi.org/10.1126/sciadv.aeb6961},
pmid = {42139357},
pmcid = {PMC13178568}
}

RIS

TY - JOUR
AU - Liu, E
AU - Xin, Xijia
AU - Shi, Mengdong
AU - Han, Weikai
AU - Ren, Qingyu
AU - Tang, Yaqi
AU - Yue, Yanan
AU - Zhang, Chenyu
AU - Gao, Zhanpeng
AU - Yue, Qingwei
AU - Sun, Jinhao
TI - Hcn1-dependent engram neurons in the PVN encode gastric inflammatory sensitization
T2 - Science advances
J2 - Sci Adv
PY - 2026
DA - 2026/05/15
VL - 12
IS - 20
SP - eaeb6961
SN - 2375-2548
PB - American Association for the Advancement of Science
DO - 10.1126/sciadv.aeb6961
UR - https://doi.org/10.1126/sciadv.aeb6961
LA - en
ER -

CSL-JSON

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