OSCR

The Drosophila connectome reveals axo-axonic synapses on descending neurons.

Overview

Authors: Cesar Ceballos1, Juan Lopez1, Ty Roachford1, Daniel Sanchez1, Sabrina Jara1, Kelli Robbins1, Casey L Spencer2, Rodney Murphey1, Rodrigo FO Pena1
ORCID iDs: Rodney Murphey
  1. Department of Biological Sciences, Florida Atlantic University, Jupiter, FL 33458, USA
  2. Harriet Wilkes Honors College, Florida Atlantic University, Jupiter, FL 33458, USA
Institutions: Florida Atlantic University (United States)
Journal: iScience, volume 29, issue 5, article 115624
Dates: received 15 September 2025; accepted 10 February 2026; published online 22 April 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1016/j.isci.2026.115624 · PMID 42063566 · PMCID PMC13126034 · OpenAlex W7151566938
Open access: gold, a free copy (OpenAlex)
Status: code verified
Categories: drosophila (organism), cellular / molecular (subfield)
Methods: Statistics, Evoked potentials, Connectivity, Graphs
Keywords: biological sciences, neuroscience, neuroanatomy
Topic: Axon Guidance and Neuronal Signaling (Cellular and Molecular Neuroscience, Neuroscience), according to OpenAlex
Funding: U.S. Department of Education (P116H230018); International Brain Research Organization
Citations: not cited yet (Europe PMC); 63 references in the paper
Research resources: Rabbit anti-GFP RRID:AB_221569, Mouse anti-Bruchpilot (nc82) RRID:AB_2314866, Goat anti-rabbit secondary RRID:AB_2338021, RRID:AB_2338902, RRID:AB_528122, RRID:BDSC_32194, RRID:BDSC_55136, RRID:BDSC_89495, MATLAB RRID:SCR_001622, Brian2 RRID:SCR_002998, Python RRID:SCR_008394, Clampex software (version 10 and 11) RRID:SCR_011323, Inkscape RRID:SCR_014479, NetworkX RRID:SCR_016864, Jupyter Notebook RRID:SCR_018315, Anaconda RRID:SCR_025572

Abstract

Axo-axonic synapses can veto, amplify, or synchronize spikes, yet their circuit-scale logic is unknown. Using the complete electron microscopy connectome of the adult male Drosophila, we charted every axo-axonic input onto the 1,314 descending neurons that carry brain commands to the ventral nerve cord. By definition, any synapse connected to a descending neuron within the cord is axo-axonic. Thus, we uncovered the ascending-descending and interneurons-descending axo-axonic relationship. Neurons with many partners (high-degree) integrate into the network without clustering into an interconnected “rich-club” of hubs. We identified an octet of ascending neurons (AN08B098) whose axo-axonic input to the giant fibers (DNp01) predicted modulation of the escape circuit. Immunostaining confirms their cholinergic identity, while optogenetic activation confirmed that this excitatory cohort increases DNp01 excitability, validating connectome-derived rules. Our work delivers a map of axo-axonic wiring in a complete ventral nerve cord connectome and provides constraints for models of fast motor control.

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

Code

No file of the authors' code could be read here: it is described below, and read at its source.

pena-rodrigo/ceballos_et_al2026_iscience

License: none: the authors keep all their rights
State: the link answers, verified on 29 September 2026
Evidence: files inventoried
Commit: c8d36e2675de650f79b18b9f21e45a31d7328f91, 9 March 2026
Size: 1 file
Software Heritage: not archived
Found in: “Data and code availability”
Not found: README, license file, CITATION.cff, environment file, tests, continuous integration, documentation
Availability: 1 check, the latest on 29 September 2026: the link answers
  • 29 September 2026: the link answers

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;
  • 0 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

Datasets cited

Data and code availability

Electrophysiology recordings have been deposited as.abf files at Mendeley Data: De Oliveira Pena, Rodrigo (2026), “ceballos2026_ephys_data”, Mendeley Data, V1 https://data.mendeley.com/datasets/dh4vghvtpm/1.

All original code used to create the connectome simulation is publicly available at GitHub: https://github.com/pena-rodrigo/ceballos_et_al2026_iscience.

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, 29 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 9 authors, 3 keywords, 2 funders, 60 references, 16 RRIDs.

Cite

This paper

Ceballos, C., Lopez, J., Roachford, T., Sanchez, D., Jara, S., Robbins, K., Spencer, C. L., Murphey, R., & Pena, R. F. (2026). The Drosophila connectome reveals axo-axonic synapses on descending neurons. iScience, 29(5), 115624. https://doi.org/10.1016/j.isci.2026.115624

BibTeX

@article{ceballos2026drosophila,
author = {Ceballos, Cesar and Lopez, Juan and Roachford, Ty and Sanchez, Daniel and Jara, Sabrina and Robbins, Kelli and Spencer, Casey L and Murphey, Rodney and Pena, Rodrigo FO},
title = {{The Drosophila connectome reveals axo-axonic synapses on descending neurons}},
journal = {iScience},
year = {2026},
month = apr,
volume = {29},
number = {5},
pages = {115624},
publisher = {Elsevier},
issn = {2589-0042},
doi = {10.1016/j.isci.2026.115624},
url = {https://doi.org/10.1016/j.isci.2026.115624},
pmid = {42063566},
pmcid = {PMC13126034}
}

RIS

TY - JOUR
AU - Ceballos, Cesar
AU - Lopez, Juan
AU - Roachford, Ty
AU - Sanchez, Daniel
AU - Jara, Sabrina
AU - Robbins, Kelli
AU - Spencer, Casey L
AU - Murphey, Rodney
AU - Pena, Rodrigo FO
TI - The Drosophila connectome reveals axo-axonic synapses on descending neurons
T2 - iScience
J2 - iScience
PY - 2026
DA - 2026/04/22
VL - 29
IS - 5
SP - 115624
SN - 2589-0042
PB - Elsevier
DO - 10.1016/j.isci.2026.115624
UR - https://doi.org/10.1016/j.isci.2026.115624
LA - en
ER -

CSL-JSON

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