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Neuron-derived neurotrophic factor-positive interneurons: a cellular target for anti-seizure therapies.

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Paper

Loaded from Europe PMC by your browser, not stored by OSCR: doi.org · Europe PMC

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The authors' code

Shell · 2 lines · 114 B · GPL-3.0

  1. #!/bin/bash
  2. gnome-terminal -e "bash -c \"source activate pyecog2PySide; python -m pip install -e . ; exec bash\""

LinuxInstall.sh at commit 0199941, under GPL-3.0 · at the source

Overview

Authors: Amy Richardson1, Marion S. Mercier1, Yoshiteru Shimoda1, Robert T. Graham1, Marco Leite1, Alejandro Garcia1, Maud Muller1, Suraya A. Bond1, Maria Grozdanova1, Qimin Wu1, Andreas Lieb1, Dimitri M. Kullmann1, Vincent Magloire1
  1. UCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, United Kingdom
Institutions: UCL Queen Square Institute of Neurology (United Kingdom); University College London (United Kingdom)
Journal: EBioMedicine, volume 130, article 106362
Dates: received 15 December 2025; accepted 16 June 2026; published online 21 July 2026; in print August 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1016/j.ebiom.2026.106362 · PMID 42475878 · PMCID PMC13393760 · OpenAlex W7169785465
Open access: gold, a free copy (OpenAlex)
Status: code verified
Categories: mouse (organism), epilepsy (population)
Methods: Spectral & time-frequency, Connectivity, Statistics, Machine learning, Evoked potentials, fMRI & imaging, Single-unit activity, calcium imaging, Physiology & signal measures
Keywords: NDNF+ interneurons, Epilepsy, Inhibition, Anti-seizure therapies
MeSH: Interneurons*, Nerve Growth Factors*, Seizures*, Animals, Calcium, Chemogenetics, Disease Models, Animal, Hippocampus, Mice, Mice, Transgenic, Optogenetics, Pyramidal Cells (* major topic)
Topic: Nerve injury and regeneration (Cellular and Molecular Neuroscience, Neuroscience), according to OpenAlex
Funding: Epilepsy Research UK (F1901, 2303F); UK Medical Research Council (MR/V034758/1, MR/W005204/1); Wellcome Trust (212285/Z/18/Z); Gatsby Charitable Foundation (GAT3955); Rosetrees Trust (CSeedcorn2021\100113); Wellcome Career Development Award (227269/Z/23/Z); Japan Epilepsy Research Foundation
Citations: not cited yet (Europe PMC); 88 references in the paper
Research resources: Anti-vasoactive intestinal polypeptide RRID:AB_10730725, Anti-somatostatin RRID:AB_10903864, Alexafluor594 anti-rabbit RRID:AB_141359, Anti-reelin RRID:AB_1603148, Anti-neuropeptide Y RRID:AB_2307354, Alexafluor568 anti-rabbit RRID:AB_2534017, Alexafluor488 anti-mouse RRID:AB_2534069, Alexafluor568 anti-mouse RRID:AB_2534072, RRID:AB_3718175, Anti-parvalbumin RRID:AB_477329, pAAV-CAG-FLEX-ArchT-GFP RRID:Addgene_28307, RRID:Addgene_44361, RRID:Addgene_62725, RRID:Addgene_83899, RRID:IMSR_JAX_008069, RRID:IMSR_JAX_012569, 29 mice) and SOM::Cre RRID:IMSR_JAX_018973, RRID:IMSR_JAX_028536, RRID:SCR_001622, RRID:SCR_002798, RRID:SCR_008394, recorded using WinEDR RRID:SCR_014270, RRID:SCR_014713

Abstract

Background: Failure of epilepsy pharmacotherapy is common, justifying efforts to identify optimal cell targets for advanced therapies. Genetic manipulations of the inhibitory system in principle offer a finely tuned intervention that cannot be achieved with a broad reduction of pyramidal neuron excitability. In this context, neuron-derived neurotrophic factor-expressing (NDNF+) interneurons evoke long-lasting GABAA and GABAB receptor-mediated inhibition. However, their contribution to restraining hyperexcitability during epileptiform activity remains unexplored.

Methods: To address this, we employed calcium imaging, optogenetics, and chemogenetics in an NDNF-Cre mouse line to investigate how NDNF+ interneurons influence cortical and hippocampal hyperactivity and spontaneous seizures.

Findings: We show that NDNF+ interneurons are actively recruited during interictal spikes and focal seizures, although more slowly than parvalbumin-positive interneurons (mean difference: 2.8 s, p = 0.023). Optogenetic hyperpolarisation of NDNF+ interneurons exacerbates epileptic discharges (normalised seizure-duration mean difference: 0.23, p = 0.0474), whereas their depolarisation suppresses focal seizures, even when the optogenetic stimulus is delayed by several seconds from seizure onset (normalized seizure-duration mean difference: −0.27, p = 0.03). This effect is largely mediated by GABAB receptors. Additionally, chemogenetic depolarisation of NDNF+ interneurons has an important anti-seizure effect in the hippocampus both ex vivo (normalised seizure-duration mean difference: −0.92, p < 0.001) and in vivo.

Interpretation: Collectively, these findings establish NDNF+ neurons as key regulators of both cortical and hippocampal excitability even during epileptic activity, and identify them as promising cellular targets for the development of anti-seizure therapies.

Funding: Epilepsy Research UK, Wellcome, the Medical Research Council, the Gatsby Charitable Foundation, and The Rosetrees Trust.

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

Repository

Its files are read in the Code ↔ Paper reader above.

KullmannLab/pyecog2

License: GPL-3.0
State: the link answers, verified on 27 September 2026
Evidence: files inventoried
Commit: 01999410e87c53f41c8b7d9d5ade0e70722dd057, 4 November 2025
Languages: Python (52), Jupyter (14), Shell (2)
Size: 134 files, 68 scripts
Software Heritage: not archived
Found in: “Data sharing statement”
Holds: README, license file, environment (setup.py), tests, 14 notebooks
Not found: CITATION.cff, continuous integration, documentation
Tools: NumPy (38 files), SciPy (17 files), Matplotlib (11 files), Numba (11 files), pandas (7 files), h5py (4 files), scikit-learn (1 file)
Availability: 1 check, the latest on 27 September 2026: the link answers
  • 27 September 2026: the link answers
70 files

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:

  • 1 repository of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
  • 68 scripts, 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

No dataset and no data link were found in the paper.

Data sharing statement

The datasets generated and analysed during this study are available from the corresponding authors upon reasonable request (email: ; ; ). PyECoG software is available at: https://github.com/KullmannLab/pyecog2.

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

Versions

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Version 2, 28 September 2026

  • Authors: added Qimin Wu (0009-0003-8879-9119); Vincent Magloire (0000-0003-4006-7042); removed Qimin Wu; Vincent Magloire

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 13 authors, 4 keywords, 12 MeSH terms, 7 funders, 87 references, 23 RRIDs.

Cite

This paper

Richardson, A., Mercier, M. S., Shimoda, Y., Graham, R. T., Leite, M., Garcia, A., Muller, M., Bond, S. A., Grozdanova, M., Wu, Q., Lieb, A., Kullmann, D. M., & Magloire, V. (2026). Neuron-derived neurotrophic factor-positive interneurons: a cellular target for anti-seizure therapies. EBioMedicine, 130, 106362. https://doi.org/10.1016/j.ebiom.2026.106362

BibTeX

@article{richardson2026neuron,
author = {Richardson, Amy and Mercier, Marion S. and Shimoda, Yoshiteru and Graham, Robert T. and Leite, Marco and Garcia, Alejandro and Muller, Maud and Bond, Suraya A. and Grozdanova, Maria and Wu, Qimin and Lieb, Andreas and Kullmann, Dimitri M. and Magloire, Vincent},
title = {{Neuron-derived neurotrophic factor-positive interneurons: a cellular target for anti-seizure therapies}},
journal = {EBioMedicine},
year = {2026},
month = jul,
volume = {130},
pages = {106362},
publisher = {Elsevier},
issn = {2352-3964},
doi = {10.1016/j.ebiom.2026.106362},
url = {https://doi.org/10.1016/j.ebiom.2026.106362},
pmid = {42475878},
pmcid = {PMC13393760}
}

RIS

TY - JOUR
AU - Richardson, Amy
AU - Mercier, Marion S.
AU - Shimoda, Yoshiteru
AU - Graham, Robert T.
AU - Leite, Marco
AU - Garcia, Alejandro
AU - Muller, Maud
AU - Bond, Suraya A.
AU - Grozdanova, Maria
AU - Wu, Qimin
AU - Lieb, Andreas
AU - Kullmann, Dimitri M.
AU - Magloire, Vincent
TI - Neuron-derived neurotrophic factor-positive interneurons: a cellular target for anti-seizure therapies
T2 - EBioMedicine
J2 - EBioMedicine
PY - 2026
DA - 2026/07/21
VL - 130
SP - 106362
SN - 2352-3964
PB - Elsevier
DO - 10.1016/j.ebiom.2026.106362
UR - https://doi.org/10.1016/j.ebiom.2026.106362
LA - en
ER -

CSL-JSON

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