Evidence map›Paper›PMID 41045929›Full record

ArticleNeuron2025

Segregated supramammillary-dentate gyrus circuits modulate cognitive and affective function in healthy and Alzheimer's disease model mice.

Yan-Jia Luo, Longfei Li, Ze-Ka Chen, Ping Dong, Ling Xie, W Todd Farmer, Qing-Song Yu, Lian-Xiang Jiang, Wei-Kun Su, Hong-Shan Liu and 15 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuron, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Glial Cells in Behavioral and Psychological Symptoms of Alzheimer's Disease.International journal of molecular sciences · 2026
    Review
  4. Article
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors.

Yan-Jia LuoDepartment of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Longfei LiHefei National Research Center for Physical Sciences at the Microscale, CAS Key Laboratory of Brain Function and Disease, Biomedical Sciences and Health Laboratory of Anhui Province, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China.
Ze-Ka ChenDepartment of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Ping DongDepartment of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Ling XieDepartment of Biochemistry & Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
W Todd FarmerDepartment of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Qing-Song YuDepartment of Gastroenterology, Songjiang Hospital and Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders, State Key Laboratory of Eye Health, Shanghai Jiao Tong University School of Medicine, Shanghai 201600, China.
Lian-Xiang JiangDepartment of Gastroenterology, Songjiang Hospital and Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders, State Key Laboratory of Eye Health, Shanghai Jiao Tong University School of Medicine, Shanghai 201600, China.
Wei-Kun SuDepartment of Gastroenterology, Songjiang Hospital and Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders, State Key Laboratory of Eye Health, Shanghai Jiao Tong University School of Medicine, Shanghai 201600, China.
Hong-Shan LiuDepartment of Gastroenterology, Songjiang Hospital and Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders, State Key Laboratory of Eye Health, Shanghai Jiao Tong University School of Medicine, Shanghai 201600, China.
Hua-Zhi WangDepartment of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Zhuo-Lei JiaoInstitute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China.
David James MelvilleDepartment of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Emma PenelDepartment of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Ryan N SheehyDepartment of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Taylor LandryDepartment of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Jing WangDepartment of Gastroenterology, Songjiang Hospital and Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders, State Key Laboratory of Eye Health, Shanghai Jiao Tong University School of Medicine, Shanghai 201600, China.
Hong JiangDepartment of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Xiao-Hong XuInstitute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China.
Xian ChenDepartment of Biochemistry & Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Nan-Jie XuDepartment of Gastroenterology, Songjiang Hospital and Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders, State Key Laboratory of Eye Health, Shanghai Jiao Tong University School of Medicine, Shanghai 201600, China; Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: xunanjie@sjtu.edu.cn.
Tian XueHefei National Research Center for Physical Sciences at the Microscale, CAS Key Laboratory of Brain Function and Disease, Biomedical Sciences and Health Laboratory of Anhui Province, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China. Electronic address: xuetian@ustc.edu.cn.
Tian-Le XuDepartment of Gastroenterology, Songjiang Hospital and Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders, State Key Laboratory of Eye Health, Shanghai Jiao Tong University School of Medicine, Shanghai 201600, China; Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: xu-happiness@shsmu.edu.cn.
Ya-Dong LiDepartment of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Gastroenterology, Songjiang Hospital and Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders, State Key Laboratory of Eye Health, Shanghai Jiao Tong University School of Medicine, Shanghai 201600, China; School of Nursing, Shanghai Jiao Tong University, Shanghai 200025, China. Electronic address: yadlee@sjtu.edu.cn.
Juan SongDepartment of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: juansong@email.unc.edu.

Funding

Regulation and functional contribution of hypothalamic modified adult hippocampal neurogenesisR01MH132222 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SONG, JUAN · 2023 to 2025
$2.3M
Enhancing adult-born neurons to restore brain functions in Alzheimer's diseaseR01AG084207 · NIA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SONG, JUAN · 2023 to 2025
$2.1M
Glutamatergic neural circuit modulation for treating Alzheimer’s diseaseR01AG071000 · NIA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Juan Song · 2024 to 2026
$1.2M
NIA NIH HHS R01 AG071000NIA NIH HHS R01 AG084207NIMH NIH HHS R01 MH132222
6 · The paper itself

Abstract

While progressive cognitive decline is the defining feature of Alzheimer's disease (AD), many patients also develop prominent neuropsychiatric symptoms, including anxiety and depression. The circuit-level mechanisms underlying these distinct symptom domains remain poorly understood, and treatments that address both cognitive and noncognitive aspects of AD are limited. Here, we identify anatomically, molecularly, and functionally distinct subpopulations of supramammillary (SuM) neurons that project to either the dorsal or ventral dentate gyrus (dDG or vDG). These distinct SuM neurons and their SuM-DG subcircuits selectively regulate memory and emotion, respectively. In AD model mice, SuM neurons targeting dDG or vDG display aberrant activity during memory or emotional processing, and importantly, targeted optogenetic activation of SuM-dDG or SuM-vDG pathways selectively restores cognitive or affective function. These findings reveal SuM-DG subcircuits as parallel modulators of cognitive and emotional states and highlight their potential as therapeutic targets for addressing the multifaceted symptomatology of AD.

Indexed as

Alzheimer DiseaseCognitionDentate GyrusAnimalsDisease Models, AnimalEmotionsMaleMiceMice, Inbred C57BLMice, TransgenicNeural PathwaysNeuronsOptogeneticsAlzheimer’s diseaseemotionhypothalamusmemorysupramammillary-dentate gyrus circuits

Identifiers

PMID41045929
PMCPMC12581905

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.