Neuron-derived neurotrophic factor-positive interneurons: a cellular target for anti-seizure therapies.
Paper
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The authors' code
Shell · 2 lines · 114 B · GPL-3.0
- #!/bin/bash
- 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
- UCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, United Kingdom
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
01999410e87c53f41c8b7d9d5ade0e70722dd057, 4 November 2025Availability: 1 check, the latest on 27 September 2026: the link answers
- 27 September 2026: the link answers
70 files
- LinuxInstall.sh, Shell, 2 lines
- LinuxLaunch.sh, Shell, 2 lines
- Notebooks/
Classifier Tests Multi animal.ipynb , Jupyter, 1,482 lines - Notebooks/
Classifier Tests Original.ipynb , Jupyter, 521 lines - Notebooks/
ClassifierCV.ipynb , Jupyter, 102 lines - Notebooks/
Data Report.ipynb , Jupyter, 371 lines - Notebooks/
Demo file creation 1.ipynb , Jupyter, 71 lines - Notebooks/
Demo file creation.ipynb , Jupyter, 142 lines - Notebooks/
FeatureExtractor tests.ipynb , Jupyter, 665 lines - Notebooks/
License test.ipynb , Jupyter, 140 lines - Notebooks/
Memap and demo file creation 1.ipynb , Jupyter, 149 lines - Notebooks/
Multithreading examples.ipynb , Jupyter, 268 lines - Notebooks/
Testing for gui 1.ipynb , Jupyter, 118 lines - Notebooks/
Tests for annotations.ipynb , Jupyter, 842 lines - Notebooks/
copy ndf fiels.ipynb , Jupyter, 53 lines - Notebooks/
overlap add and overlap save tests.ipynb , Jupyter, 193 lines - UnitTestFiles/
1.py , Python, 10 lines - pyecog2/
ProjectClass.py , Python, 715 lines - pyecog2/
__init__.py , Python, 1 line - pyecog2/
__main__.py , Python, 2 lines - pyecog2/
annotation_table_widget. , Python, 625 linespy - pyecog2/
annotations_module.py , Python, 420 lines - pyecog2/
classifier.py , Python, 554 lines - pyecog2/
coding_tests/ , Python, 177 linesParameterTreeExample.py - pyecog2/
coding_tests/ , Python, 109 linesParameterTreeTest.py - pyecog2/
coding_tests/ , Python, 121 linesParameterTreeTest2.py - pyecog2/
coding_tests/ , Python, 36 linesProgressBarTests.py - pyecog2/
coding_tests/ , Python, 22 linesPySide_Test.py - pyecog2/
coding_tests/ , Python, 63 linesTableTests.py - pyecog2/
coding_tests/ , Python, 30 linesTableTests2.py - pyecog2/
coding_tests/ , Python, 176 linesWPTacquisition.py - pyecog2/
coding_tests/ , Python, 1 line__init__.py - pyecog2/
coding_tests/ , Python, 109 linesdock_tests.py - pyecog2/
coding_tests/ , Python, 19 lineslogging_tests.py - pyecog2/
coding_tests/ , Python, 5 lineslogging_tests_submodule. py - pyecog2/
coding_tests/ , Python, 123 linespyqtgraph_examples.py - pyecog2/
coding_tests/ , Python, 90 linessave_settings.py - pyecog2/
coding_tests/ , Python, 32 linestesting_menu.py - pyecog2/
deprecated/ , Python, 1 line__init__.py - pyecog2/
deprecated/ , Python, 132 linesadafruit_notofications.p y - pyecog2/
deprecated/ , Python, 129 linesgui_main.py - pyecog2/
deprecated/ , Python, 268 linesold__forref_PyecogCurveP lotItem.py - pyecog2/
feature_extractor.py , Python, 201 lines - pyecog2/
h5loader.py , Python, 107 lines - pyecog2/
hmm_pyecog.py , Python, 333 lines - pyecog2/
license.py , Python, 159 lines - pyecog2/
logging_aux.py , Python, 24 lines - pyecog2/
main.py , Python, 850 lines - pyecog2/
ndf_converter.py , Python, 761 lines - pyecog2/
paired_graphics_view.py , Python, 739 lines - pyecog2/
pyecog_plot_item.py , Python, 509 lines - pyecog2/
pyqtgraph_classes.py , Python, 1 line - pyecog2/
special_features.py , Python, 19 lines - pyecog2/
spectrotools.py , Python, 241 lines - pyecog2/
tree_model_and_nodes.py , Python, 431 lines - pyecog2/
tree_widget.py , Python, 219 lines - pyecog2/
ui_elements/ , Python, 188 linesAnnotationParameterTree. py - pyecog2/
ui_elements/ , Python, 410 linesClassifierGUI.py - pyecog2/
ui_elements/ , Python, 96 linesFFTWidget.py - pyecog2/
ui_elements/ , Python, 251 linesFeatureExtractorGUI.py - pyecog2/
ui_elements/ , Python, 270 linesNDFConverterGUI.py - pyecog2/
ui_elements/ , Python, 132 linesPlotControlsWidget.py - pyecog2/
ui_elements/ , Python, 247 linesProjectGUI.py - pyecog2/
ui_elements/ , Python, 254 linesVideoPlayerWidget.py - pyecog2/
ui_elements/ , Python, 489 linesWaveletWidget.py - pyecog2/
ui_elements/ , Python, 1 line__init__.py - pyecog2/
ui_elements/ , Python, 44 linespyecogParameterTree.py - setup.py, Python, 36 lines
- LICENSE, License, 674 lines
- README.md, Text, 29 lines
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;
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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://
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://
BibTeX
@article{richardson2026n
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/
url = {https://
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/
VL - 130
SP - 106362
SN - 2352-3964
PB - Elsevier
DO - 10.1016/
UR - https://
LA - en
ER -
CSL-JSON
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