Evidence map›Paper›PMID 41485044›Full record

ArticleMolecular neurodegeneration2026

Developmental dopamine loss rewires striatal circuits to promote locomotion.

Jie Dong, Breanna T Sullivan, Victor M Martinez Smith, Lupeng Wang, Lulu Tian, Justin Kung, Bin Song, Shirong Lin, Andreanna Le, Lixin Sun and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular neurodegeneration, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Jie DongTransgenics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35, Room 1A112, MSC 3707, 35 Convent Drive, Bethesda, MD, 20892-3707, USA.
Breanna T SullivanTransgenics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35, Room 1A112, MSC 3707, 35 Convent Drive, Bethesda, MD, 20892-3707, USA.
Victor M Martinez SmithTransgenics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35, Room 1A112, MSC 3707, 35 Convent Drive, Bethesda, MD, 20892-3707, USA.
Lupeng WangTransgenics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35, Room 1A112, MSC 3707, 35 Convent Drive, Bethesda, MD, 20892-3707, USA.
Lulu TianTransgenics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35, Room 1A112, MSC 3707, 35 Convent Drive, Bethesda, MD, 20892-3707, USA.
Justin KungTransgenics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35, Room 1A112, MSC 3707, 35 Convent Drive, Bethesda, MD, 20892-3707, USA.
Bin SongTransgenics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35, Room 1A112, MSC 3707, 35 Convent Drive, Bethesda, MD, 20892-3707, USA.
Shirong LinTransgenics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35, Room 1A112, MSC 3707, 35 Convent Drive, Bethesda, MD, 20892-3707, USA.
Andreanna LeTransgenics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35, Room 1A112, MSC 3707, 35 Convent Drive, Bethesda, MD, 20892-3707, USA.
Lixin SunTransgenics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35, Room 1A112, MSC 3707, 35 Convent Drive, Bethesda, MD, 20892-3707, USA.
Lisa ChangTransgenics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35, Room 1A112, MSC 3707, 35 Convent Drive, Bethesda, MD, 20892-3707, USA.
Jinhui DingComputational Biology Group, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, 20892, USA.
Weidong LeNeurology Program, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China. wdle@sibs.ac.cn.
Jun JiaTransgenics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35, Room 1A112, MSC 3707, 35 Convent Drive, Bethesda, MD, 20892-3707, USA.
Huaibin CaiTransgenics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35, Room 1A112, MSC 3707, 35 Convent Drive, Bethesda, MD, 20892-3707, USA. caih@mail.nih.gov.

Funding

Molecular and Pathophysiological Study of Parkinson's DiseaseZIAAG000928 · NIA · NATIONAL INSTITUTE ON AGING · PI CAI, HUAIBIN · 2011 to 2025
$15.8M
Intramural NIH HHS ZIA AG000928
6 · The paper itself

Abstract

backgroundMotor symptoms of Parkinson’s disease (PD) primarily result from the degeneration of nigrostriatal dopaminergic neurons (DANs), particularly the Aldehyde Dehydrogenase 1A1-positive (ALDH1A1⁺) subpopulation. Pitx3-deficient mice exhibit selective developmental loss of ALDH1A1⁺ DANs but paradoxically display hyperlocomotion, suggesting compensatory changes in striatal circuitry. The dorsal striatum contains four main types of spiny projection neurons (SPNs): patch (or striosome) and matrix subtypes of both direct-pathway (dSPNs) and indirect-pathway (iSPNs). Activation of patch dSPNs suppresses locomotion by inhibiting ALDH1A1⁺ DANs.

methodsWe combined RNAscope in situ hybridization with SPN subtype-specific reporter mice to quantify patch and total dSPNs and iSPNs in Pitx3-deficient and control mice. Three patch SPN reporter lines (Kremen12A − Cre, Nr4a1-GFP, and PdynIRES−Cre) were used to map projections. Optogenetic stimulation was performed in freely moving mice to assess the behavioral effects of activating patch dSPNs and iSPNs.

resultsPitx3-deficient mice showed no change in the overall dSPN: iSPN ratio but exhibited a marked shift in the patch dSPN: patch iSPN ratio, which decreased from 1.7 in control mice to 0.7 in the Pitx3-deficient group. Accordingly, patch dSPN projections to the substantia nigra pars reticulata (SNr) were reduced, whereas patch iSPN projections to the globus pallidus externus (GPe) were enhanced. Notably, while optogenetic stimulation of patch dSPNs and iSPNs suppressed locomotion in control mice, the same stimulation promoted locomotion in Pitx3-deficient mice.

conclusionsOur findings reveal a selective reorganization of patch SPNs in response to developmental loss of ALDH1A1⁺ DANs, characterized by reduced patch dSPN and enhanced patch iSPN influence. This shift may underlie the paradoxical hyperlocomotion observed in Pitx3-deficient mice and provides insight into circuit-level adaptations with potential therapeutic relevance for PD.

Indexed as

Corpus StriatumDopamineDopaminergic NeuronsLocomotionAldehyde Dehydrogenase 1 FamilyAnimalsHomeodomain ProteinsMedium Spiny NeuronsMiceParkinson DiseaseRetinal DehydrogenaseSubstantia NigraTranscription FactorsAldehyde Dehydrogenase 1 FamilyALDH1A1 protein, mouseDopaminehomeobox protein PITX3Homeodomain ProteinsRetinal DehydrogenaseTranscription FactorsALDH1A1Direct-pathwayDopaminergic neuronsIndirect-pathwayKremen1Optogenetics, and NeuromodulationParkinson’s diseasePitx3Striatal projection neurons

Identifiers

PMID41485044
PMCPMC12866494

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.