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Astrocytes mediate the dopaminergic modulation of tonic GABAergic signaling in substantia nigra.

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Code Sample.nb, under CC-BY-4.0 · at the source

Overview

Authors: DeNard V. Simmons1,2, Oscar Andrés Moreno-Ramos3,2, Divya D. A. Raj3,2, Konstantin Kaganovsky4, Arin Pamukcu1,2, Nora Vrieler1,2, Tatiana Tkatch1,2, Zhong Xie1,2, Ana Isabel Silva de Sousa1,2, Enrico Zampese1,2, Jun Ding4,2, Rajeshwar Awatramani3,2, Charles J. Wilson5, D. James Surmeier1,2
ORCID iDs: DeNard V. Simmons, Oscar Andrés Moreno-Ramos, Divya D. A. Raj, Konstantin Kaganovsky, Nora Vrieler, Tatiana Tkatch, Zhong Xie, Ana Isabel Silva de Sousa, Enrico Zampese, Jun Ding, Rajeshwar Awatramani, Charles J. Wilson, D. James Surmeier
  1. Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
  2. Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA
  3. Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
  4. Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA
  5. Department of Neuroscience, Developmental and Regenerative Biology, University of Texas at San Antonio, San Antonio, TX 78249, USA
Institutions: Northwestern University (United States); Aligning Science Across Parkinson's (United States); Stanford Medicine (United States); Stanford University (United States); The University of Texas at San Antonio (United States)
Journal: Science advances, volume 12, issue 37, article eadq8840
Dates: received 4 June 2024; accepted 31 July 2026; published online 9 September 2026; in print September 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1126/sciadv.adq8840 · PMID 42715320 · PMCID PMC13557058 · OpenAlex W7162036903
Open access: gold, a free copy (OpenAlex)
Status: code verified
Categories: mouse (organism), cellular / molecular (subfield)
Methods: Spectral & time-frequency
MeSH: Astrocytes*, Dopamine*, Dopaminergic Neurons*, gamma-Aminobutyric Acid*, Signal Transduction*, Substantia Nigra*, Aldehyde Dehydrogenase 1 Family, Animals, GABA Plasma Membrane Transport Proteins, Mice, Receptors, Dopamine D2, Receptors, GABA-A, Retinal Dehydrogenase, Synaptic Transmission (* major topic)
Journal subjects: Neuroscience, Neurophysiology
Topic: Neuroscience and Neuropharmacology Research (Cellular and Molecular Neuroscience, Neuroscience), according to OpenAlex
Funding: Department of Defense (W81XWH2110749); National Institute of Neurological Disorders and Stroke (NS121174); Aligning Science Across Parkinson’s (ASAP) (ASAP020551); Freedom Together Foundation (MR-2021-2960); Bumpus Foundation (Fellowship)
Citations: not cited yet (Europe PMC); 73 references in the paper
Research resources: AAV9-hSyn-DIO-hM4Di-mCherry RRID:Addgene_44362, AAV9-hSyn-hM4Di-mCherry RRID:Addgene_50475, AAV2/5-GfAABC1D-hM3Dg-mCherry RRID:Addgene_50478, RRID:SCR_002285, RRID:SCR_017142

Abstract

Recent studies have implicated dopaminergic signaling within the substantia nigra pars reticulata (SNr) in the emergence of Parkinsonian motor deficits. To better understand the mechanisms underlying this dependence, the ability of dopamine to modulate SNr neuron activity was studied in ex vivo mouse brain slices. In addition to presynaptically inhibiting phasic GABA release, D2 dopamine receptor (D2R) signaling unexpectedly suppressed a tonic, GABAA receptor–mediated inhibition of SNr neuron spiking. Our studies demonstrated that this tonic modulation was largely mediated by GAT-1–dependent GABA release from ALDH1A1-expressing dopaminergic neurons. In contrast, the ability of D2R agonists to disinhibit SNr neurons depended on D2R-expressing astrocytes and stimulation of GAT-3 uptake of GABA from the extracellular space. In addition to underscoring the importance of dendritically released dopamine in modulating synaptic transmission, our studies demonstrate that dopaminergic modulation of astrocytes plays a key role in modulating SNr circuits and motor behavior.

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

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Zenodo 10855006

License: CC-BY-4.0
State: the link answers, verified on 26 September 2026
Evidence: files inventoried
Languages: Mathematica (1)
Size: 1 file, 1 script
Software Heritage: not checked
Found in: “Data, code, and materials availability:”
Holds: 1 notebook
Not found: README, license file, CITATION.cff, environment file, tests, continuous integration, documentation
Availability: 1 check, the latest on 26 September 2026: the link answers (HTTP 200)
  • 26 September 2026: the link answers (HTTP 200)
1 file
At the source: doi.org/10.5281/zenodo.10855006

Zenodo 17296457

License: CC-BY-4.0
State: the link answers, verified on 26 September 2026
Evidence: files inventoried
Size: 1 file, 0 scripts
Software Heritage: not checked
Found in: “Data, code, and materials availability:”
Not found: README, license file, CITATION.cff, environment file, tests, continuous integration, documentation
Availability: 1 check, the latest on 26 September 2026: the link answers (HTTP 200)
  • 26 September 2026: the link answers (HTTP 200)
At the source: doi.org/10.5281/zenodo.17296457

The paper's code and data availability statement is in the Data section.

Tracing map

Proposed by the machine: these links were found in the paper and verified at the source, without human review. The map will receive a Zenodo DOI once one of the paper's authors has validated it with their ORCID.

What the map holds:

  • 2 repositories of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
  • 1 script, each with its path and the digest of its content;
  • no match between paragraphs and code yet;
  • neither the text of the paper nor the code itself.

Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.

Data

Datasets cited

Data, code, and materials availability

All datasets (https://doi.org/10.5281/zenodo.10850896), protocols, key lab materials used, and code generated (https://doi.org/10.5281/zenodo.10855006) in this study are listed in a key resource table (https://doi.org/10.5281/zenodo.17296457) alongside their public persistent identifiers. This study did not generate new materials.

Reproduced under the paper's license (CC BY), 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, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 14 authors, 14 MeSH terms, 5 funders, 73 references, 5 RRIDs.

Cite

This paper

Simmons, D. V., Moreno-Ramos, O. A., Raj, D. D. A., Kaganovsky, K., Pamukcu, A., Vrieler, N., Tkatch, T., Xie, Z., de Sousa, A. I. S., Zampese, E., Ding, J., Awatramani, R., Wilson, C. J., & Surmeier, D. J. (2026). Astrocytes mediate the dopaminergic modulation of tonic GABAergic signaling in substantia nigra. Science advances, 12(37), eadq8840. https://doi.org/10.1126/sciadv.adq8840

BibTeX

@article{simmons2026astrocytes,
author = {Simmons, DeNard V. and Moreno-Ramos, Oscar Andrés and Raj, Divya D. A. and Kaganovsky, Konstantin and Pamukcu, Arin and Vrieler, Nora and Tkatch, Tatiana and Xie, Zhong and de Sousa, Ana Isabel Silva and Zampese, Enrico and Ding, Jun and Awatramani, Rajeshwar and Wilson, Charles J. and Surmeier, D. James},
title = {{Astrocytes mediate the dopaminergic modulation of tonic GABAergic signaling in substantia nigra}},
journal = {Science advances},
year = {2026},
month = sep,
volume = {12},
number = {37},
pages = {eadq8840},
publisher = {American Association for the Advancement of Science},
issn = {2375-2548},
doi = {10.1126/sciadv.adq8840},
url = {https://doi.org/10.1126/sciadv.adq8840},
pmid = {42715320},
pmcid = {PMC13557058}
}

RIS

TY - JOUR
AU - Simmons, DeNard V.
AU - Moreno-Ramos, Oscar Andrés
AU - Raj, Divya D. A.
AU - Kaganovsky, Konstantin
AU - Pamukcu, Arin
AU - Vrieler, Nora
AU - Tkatch, Tatiana
AU - Xie, Zhong
AU - de Sousa, Ana Isabel Silva
AU - Zampese, Enrico
AU - Ding, Jun
AU - Awatramani, Rajeshwar
AU - Wilson, Charles J.
AU - Surmeier, D. James
TI - Astrocytes mediate the dopaminergic modulation of tonic GABAergic signaling in substantia nigra
T2 - Science advances
J2 - Sci Adv
PY - 2026
DA - 2026/09/09
VL - 12
IS - 37
SP - eadq8840
SN - 2375-2548
PB - American Association for the Advancement of Science
DO - 10.1126/sciadv.adq8840
UR - https://doi.org/10.1126/sciadv.adq8840
LA - en
ER -

CSL-JSON

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