Light- and temperature-sensitive seizures are regulated by spatially distinct cortex glial populations in the central nervous system.

Overview

Authors: Govind Kunduri¹, Tanja Angela Godenschwege², Katherine Sankey², Kandahalli Venkataranganayaka Abhilasha¹, Usha Acharya¹, Jairaj K. Acharya¹

ORCID iDs: Govind Kunduri, Tanja Angela Godenschwege, Katherine Sankey, Kandahalli Venkataranganayaka Abhilasha, Usha Acharya, Jairaj K. Acharya

Center for Cancer Research, Cancer and Developmental Biology Laboratory, National Cancer Institute, Frederick, MD 21702
Biological Sciences Department, Florida Atlantic University, Jupiter, FL 33458

Institutions: National Cancer Institute (Ukraine); National Cancer Institute (Malaysia); National Cancer Institute (United States); Center for Cancer Research (United States); Florida Atlantic University (United States)

Journal: Proceedings of the National Academy of Sciences of the United States of America, volume 123, issue 30, article e2605750123

Dates: received 20 February 2026; accepted 22 June 2026; published online 21 July 2026; in print 28 July 2026

Type: Research article · Language: English

License: CC BY

Identifiers: DOI 10.1073/pnas.2605750123 · PMID 42479834 · PMCID PMC13417042 · OpenAlex W4411754904

Open access: hybrid, a free copy (OpenAlex)

Preprint: doi:10.1101/2025.06.27.661959

Status: code on request

Categories: drosophila (organism), epilepsy (population), cellular / molecular (subfield)

Keywords: glia, epilepsy, sphingolipids, glial heterogeneity

MeSH: Central Nervous System*, Cerebral Cortex*, Neuroglia*, Seizures*, Animals, Drosophila melanogaster, Drosophila Proteins, Light, Mutation, Temperature (* major topic)

Journal subjects: Biological Sciences, Neuroscience

Topic: Photoreceptor and optogenetics research (Cellular and Molecular Neuroscience, Neuroscience), according to OpenAlex

Funding: Department of Human Health and Services (ZIABC010331-25)

Citations: not cited yet (Europe PMC); 75 references in the paper

Abstract

Epilepsy is characterized by recurrent seizures due to abnormal neuronal activity originating from a population of neurons. Seizures are often associated with abnormal glial cell function at the seizure focus. Studies have shown that each glial type, such as astrocytes, displays a significant degree of heterogeneity in their development, molecular signatures, and function depending on the brain region in which they are located. It is unknown, however, if such heterogeneity differentially influences or causes seizures. Previous studies in Drosophila have shown that aberrant Cortex glia (CG) function led to light-inducible (LI) seizures in Ceramide phosphoethanolamine synthase (cpes) and temperature-sensitive (TS) seizures in zydeco (zyd1) mutants. Here, we have optimized Gal4/Split-Gal4/Gal80/LexA drivers to specifically express a gene of interest throughout development in CG subpopulations in different parts of the brain including optic lobe (OL), central brain (CB), and ventral nerve cord (VNC). Using these tools, we performed brain region–specific CG rescue experiments in cpes and zyd1 mutants. We found that OL- and CB-specific, but not VNC-specific CG expression of CPES significantly suppressed LI seizures in cpes mutants. In contrast, VNC- but not OL- or CB-specific CG expression of ZYD suppressed TS seizures. In a third model, expression and activation of transient receptor potential, dTRPA1, exclusively in the VNC-specific CG was sufficient to induce TS seizures in wild-type flies. Our findings suggest that regionally specialized CG subtypes differentially regulate seizure susceptibility in seizure models.

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

Code

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

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Data

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Data, Materials, and Software Availability

All study data are included in the article and/or supporting information (http://www.pnas.org/lookup/doi/10.1073/pnas.2605750123#supplementary-materials) and the fly stocks generated in the study are available upon request from corresponding authors. There is no new data associated with this article.

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

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 6 authors, 4 keywords, 10 MeSH terms, 1 funder, 72 references.

Cite

This paper

Kunduri, G., Godenschwege, T. A., Sankey, K., Abhilasha, K. V., Acharya, U., & Acharya, J. K. (2026). Light- and temperature-sensitive seizures are regulated by spatially distinct cortex glial populations in the central nervous system. Proceedings of the National Academy of Sciences of the United States of America, 123(30), e2605750123. https://doi.org/10.1073/pnas.2605750123

BibTeX

@article{kunduri2026light, author = {Kunduri, Govind and Godenschwege, Tanja Angela and Sankey, Katherine and Abhilasha, Kandahalli Venkataranganayaka and Acharya, Usha and Acharya, Jairaj K.}, title = {{Light- and temperature-sensitive seizures are regulated by spatially distinct cortex glial populations in the central nervous system}}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, year = {2026}, month = jul, volume = {123}, number = {30}, pages = {e2605750123}, publisher = {National Academy of Sciences}, issn = {0027-8424}, doi = {10.1073/pnas.2605750123}, url = {https://doi.org/10.1073/pnas.2605750123}, pmid = {42479834}, pmcid = {PMC13417042} }

RIS

TY - JOUR AU - Kunduri, Govind AU - Godenschwege, Tanja Angela AU - Sankey, Katherine AU - Abhilasha, Kandahalli Venkataranganayaka AU - Acharya, Usha AU - Acharya, Jairaj K. TI - Light- and temperature-sensitive seizures are regulated by spatially distinct cortex glial populations in the central nervous system T2 - Proceedings of the National Academy of Sciences of the United States of America J2 - Proc Natl Acad Sci U S A PY - 2026 DA - 2026/07/21 VL - 123 IS - 30 SP - e2605750123 SN - 0027-8424 PB - National Academy of Sciences DO - 10.1073/pnas.2605750123 UR - https://doi.org/10.1073/pnas.2605750123 LA - en ER -

CSL-JSON

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