Evidence map›Paper›PMID 41337591›Full record

ArticleScience advances2025

State-dependent modulation of spiny projection neurons controls levodopa-induced dyskinesia in a mouse model of Parkinson's disease.

Shenyu Zhai, Qiaoling Cui, David Wokosin, Linqing Sun, Tatiana Tkatch, Jill R Crittenden, Ann M Graybiel, D James Surmeier

Abstract read
In one paragraph

Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Levodopa Disrupts Activity Patterns and Encoding of Movement in Striatal Cholinergic Interneurons of Behaving Mice.Movement disorders : official journal of the Movement Disorder Society · 2025
    Article
  6. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Shenyu ZhaiDepartment of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.ORCID 0000-0002-7097-9387
Qiaoling CuiDepartment of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.ORCID 0000-0002-1632-4208
David WokosinDepartment of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.ORCID 0000-0002-5497-6944
Linqing SunDepartment of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.ORCID 0000-0002-1217-277X
Tatiana TkatchDepartment of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.ORCID 0000-0001-6626-7435
Jill R CrittendenMcGovern Institute for Brain Research and Department of Brain and Cognitive Sciences, MIT, Cambridge, MA 02139, USA.
Ann M GraybielMcGovern Institute for Brain Research and Department of Brain and Cognitive Sciences, MIT, Cambridge, MA 02139, USA.ORCID 0000-0002-4326-7720
D James SurmeierDepartment of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

Funding

DOPAMINERGIC AND MUSCARINIC SIGNALING IN THE STRIATUMR37NS034696 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI DALTON JAMES SURMEIER · 2001 to 2026
$7.3M
Determinants of Basal Ganglia Pathology in Parkinson's DiseaseR01NS121174 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI BEVAN, MARK D, SURMEIER, DALTON JAMES · 2021 to 2025
$3.6M
NINDS NIH HHS R01 NS121174NINDS NIH HHS R37 NS034696
6 · The paper itself

Abstract

In the later stages of Parkinson's disease, patients often manifest levodopa-induced dyskinesia (LID), compromising their quality of life. The pathophysiology underlying LID is poorly understood, and treatment options are limited. To move toward filling this treatment gap, the intrinsic and synaptic changes in striatal spiny projection neurons (SPNs) triggered by the sustained elevation of dopamine (DA) during dyskinesia were characterized using electrophysiological, pharmacological, molecular, and behavioral approaches. Our studies revealed that the intrinsic excitability and functional corticostriatal connectivity of SPNs in dyskinetic mice oscillate between LID on- and off-states in a cell- and state-specific manner. Although triggered by levodopa, these oscillations in SPN properties depended on both dopaminergic and cholinergic signaling. Disrupting M1 muscarinic receptor signaling specifically in indirect pathway SPNs or deleting its downstream signaling partner CalDAG-GEFI blunted the levodopa-induced alterations in functional connectivity, enhanced the motoric benefits of levodopa, and attenuated LID severity.

Indexed as

Dyskinesia, Drug-InducedLevodopaNeuronsParkinson DiseaseAnimalsAntiparkinson AgentsCorpus StriatumDisease Models, AnimalDopamineMaleMiceAntiparkinson AgentsDopamineLevodopa

Identifiers

PMID41337591
PMCPMC12674127

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Registered trials

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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.