OSCR

Cell-type-resolved RNA-seq reveals molecular signatures of sexual experience in <i>Drosophila</i> neuromodulatory neurons.

Overview

Authors: Julia Ryvkin1, Anat Shmueli1, Ayalla Aharony1, Mali Levi1, Dion Dickman2, Galit Shohat-Ophir1
ORCID iDs: Galit Shohat-Ophir
  1. The Goodman Faculty of Life Sciences, the Multidisciplinary Brain Research Center and the Institute for Nanotechnology and Advanced Materials, Bar-Ilan University, Israel
  2. Department of Neurobiology, University of Southern California, United States
Institutions: Bar-Ilan University (Israel); University of Southern California (United States)
Journal: NAR genomics and bioinformatics, volume 8, issue 3, article lqag074
Dates: received 2 November 2025; accepted 10 May 2026; published online 17 July 2026
Type: Research article · Language: English
License: CC BY-NC
Identifiers: DOI 10.1093/nargab/lqag074 · PMID 42491142 · PMCID PMC13376146 · OpenAlex W7169507390
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: genetics / omics (modality), drosophila (organism), cellular / molecular (subfield)
Methods: Statistics, Evoked potentials
MeSH: Drosophila*, Drosophila melanogaster*, Neurons*, RNA-Seq*, Sexual Behavior, Animal*, Animals, Drosophila Proteins, Male (* major topic)
Journal subjects: Computational Methods for Transcriptome Analysis
Topic: Neurobiology and Insect Physiology Research (Cellular and Molecular Neuroscience, Neuroscience), according to OpenAlex
Funding: Israel Science Foundation (174/19, 219/24); BSF (2024612); National Science Foundation (IOS-2417451)
Citations: not cited yet (Europe PMC); 133 references in the paper

Abstract

Flexible behavioral responses depend on the ability of neural circuits to adapt their physiology and output to changing social and environmental contexts. Neuromodulation is central to this flexibility, yet how specific experiences are encoded within neuromodulatory neurons remains largely unknown. Here, we show that distinct motivational outcomes drive distinct regulatory responses in three neuromodulatory neuronal populations in male Drosophila. Using cell-type-resolved RNA sequencing, we profiled serotonergic (Trh), octopaminergic/tyraminergic (Tdc2), and neuropeptide F receptor (NPFR) neurons after successful mating, sexual rejection, or social isolation. Each experience induced a unique molecular signature within each cell type. NPFR neurons showed the strongest remodeling after rejection, Tdc2 neurons preferentially represented the naïve-single state, and Trh neurons displayed balanced, experience-specific tuning. Shared differentially expressed genes were few and often oppositely regulated, indicating strong cell-type-specific transcriptional logic. Experience-dependent changes spanned multiple regulatory layers, including chromatin organization, RNA metabolism, proteostasis, metabolism, and synaptic machinery. Notably, sexual rejection engaged transcriptional programs consistent with homeostatic synaptic scaling, including coordinated upregulation of dense-core vesicle components and cAMP signaling together with reduced inhibitory tone in Tdc2 neurons, and complementary remodeling of vesicle fusion and trafficking machinery in Trh neurons. We further identified compact, population-specific rejection-associated modules that converge functionally on circadian regulation, stress responses, and metabolic pathways. Together, these findings show that motivation is encoded through distinct regulatory responses that tune neuromodulatory circuit function and support behavioral flexibility.

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

Code

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Tracing map

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Data

Datasets cited

Data availability

The data reported in this paper have been deposited in BioStudies database: Galit Shohat-Ophir & Julia Ryvkin (2025). Cell-type–resolved RNA-seq reveals molecular engrams of sexual experience in Drosophila neuromodulatory neurons. BioStudies, E-MTAB-15973. Retrieved from https://www.ebi.ac.uk/biostudies/arrayexpress/studies/E-MTAB-15973.

Reproduced under the paper's license (CC BY-NC), 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, 6 authors, 8 MeSH terms, 3 funders, 131 references.

Cite

This paper

Ryvkin, J., Shmueli, A., Aharony, A., Levi, M., Dickman, D., & Shohat-Ophir, G. (2026). Cell-type-resolved RNA-seq reveals molecular signatures of sexual experience in <i>Drosophila</i> neuromodulatory neurons. NAR genomics and bioinformatics, 8(3), lqag074. https://doi.org/10.1093/nargab/lqag074

BibTeX

@article{ryvkin2026cell,
author = {Ryvkin, Julia and Shmueli, Anat and Aharony, Ayalla and Levi, Mali and Dickman, Dion and Shohat-Ophir, Galit},
title = {{Cell-type-resolved RNA-seq reveals molecular signatures of sexual experience in \<i\>Drosophila\</i\> neuromodulatory neurons}},
journal = {NAR genomics and bioinformatics},
year = {2026},
month = jul,
volume = {8},
number = {3},
pages = {lqag074},
publisher = {Oxford University Press},
issn = {2631-9268},
doi = {10.1093/nargab/lqag074},
url = {https://doi.org/10.1093/nargab/lqag074},
pmid = {42491142},
pmcid = {PMC13376146}
}

RIS

TY - JOUR
AU - Ryvkin, Julia
AU - Shmueli, Anat
AU - Aharony, Ayalla
AU - Levi, Mali
AU - Dickman, Dion
AU - Shohat-Ophir, Galit
TI - Cell-type-resolved RNA-seq reveals molecular signatures of sexual experience in <i>Drosophila</i> neuromodulatory neurons
T2 - NAR genomics and bioinformatics
J2 - NAR Genom Bioinform
PY - 2026
DA - 2026/07/17
VL - 8
IS - 3
SP - lqag074
SN - 2631-9268
PB - Oxford University Press
DO - 10.1093/nargab/lqag074
UR - https://doi.org/10.1093/nargab/lqag074
LA - en
ER -

CSL-JSON

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"language": "en",
"issued": {
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