Evidence map›Paper›PMID 41102541›Full record

ArticleNature neuroscience2025

Differential synaptic depression mediates the therapeutic effect of deep brain stimulation.

Jicheng Li, Jingheng Zhou, Bo He, Amy B Papaneri, Nicholas P Kobzar, Alan C Yeh, Ying Zhang, Guohong Cui

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature neuroscience, 2025. 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

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

8 authors.

Jicheng LiIn Vivo Neurobiology Group, Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, Durham, NC, USA.
Jingheng ZhouIn Vivo Neurobiology Group, Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, Durham, NC, USA.ORCID http://orcid.org/0000-0003-0280-6166
Bo HeViral Vector Core, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, Durham, NC, USA.
Amy B PapaneriIn Vivo Neurobiology Group, Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, Durham, NC, USA.ORCID http://orcid.org/0000-0003-2144-2441
Nicholas P KobzarIn Vivo Neurobiology Group, Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, Durham, NC, USA.
Alan C YehIn Vivo Neurobiology Group, Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, Durham, NC, USA.
Ying ZhangDepartment of Neurology and Neuroscience Center, The First Hospital of Jilin University, Changchun, China. zhang_ying99@jlu.edu.cn.ORCID http://orcid.org/0000-0002-4448-2051
Guohong CuiIn Vivo Neurobiology Group, Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, Durham, NC, USA. cuig@mail.nih.gov.ORCID http://orcid.org/0000-0002-4555-028X

Funding

Basal Ganglia in Health and DiseaseZIAES103310 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI CUI, GUOHONG · 2016 to 2025
$23.6M
Intramural NIH HHS ZIA ES103310National Natural Science Foundation of China (National Science Foundation of China) Nos:81974194U.S. Department of Health & Human Services | NIH | National Institute of Environmental Health Sciences (NIEHS) ZIA-ES103310
6 · The paper itself

Abstract

Deep brain stimulation (DBS) effectively treats drug-resistant neurological and psychiatric disorders, yet its mechanisms remain unclear. Here we show that high-frequency DBS of the subthalamic nucleus (STN), a common target for Parkinson's disease (PD), activates afferent axons while inhibiting STN neurons. These contrasting presynaptic and postsynaptic effects arise from a decrease in local neurotransmitter release with a larger decrease in glutamate than GABA, shifting the excitation/inhibition balance toward inhibition. Chemogenetic inhibition, but not excitation, of STN neurons mimics the therapeutic effects of DBS in 6-OHDA-lesioned PD mice. Acute and chronic bilateral chemogenetic STN inhibition restores motor function in a progressive PD mouse model. These findings suggest that inhibition of STN, caused by differential depression of glutamatergic and GABAergic synapses, is a key mechanism of therapeutic DBS. 'Chemogenetic DBS', direct chemogenetic inhibition of postsynaptic neurons, may offer a less invasive and more affordable alternative to electrical DBS for PD and other neurological disorders.

Indexed as

Deep Brain StimulationSubthalamic NucleusSynapsesAnimalsDisease Models, Animalgamma-Aminobutyric AcidGlutamic AcidMaleMiceMice, Inbred C57BLNeuronsOxidopaminegamma-Aminobutyric AcidGlutamic AcidOxidopamine

Identifiers

PMID41102541
PMCPMC12672378

What OpenQuestion holds

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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.