Nitric oxide refines retinal circuit architecture independently of retinal wave dynamics.
Overview
- Centro de Matemática, Computação e Cognição, Universidade Federal do ABC, São Bernardo do Campo, SP Brazil
- Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, SP Brazil
- Institute of Physics, Humboldt University at Berlin, Berlin, Germany
Abstract
How diffusible neuromodulators control neural circuit assembly remains a key open question in neuroscience. While nitric oxide (NO) is known to regulate mature synaptic plasticity, its role during development, specifically whether it shapes circuits through activity-dependent or activity-independent pathways, has not been fully understood. Here, we combine ultrasensitive electron paramagnetic resonance (EPR) spectroscopy, 4096-channel high-density multielectrode array (HD-MEA) recordings, and advanced graph-theoretical analysis to study how NO contributes to retinal network formation during a critical period of synaptogenesis. In the rat retina, nNOS expression begins at postnatal day 10 in two distinct amacrine cell subtypes, coinciding with the first detectable NO production. Acute or selective nNOS inhibition preserved the spatiotemporal features of Stage III retinal waves but significantly changed network topology, increasing network degree and density. Molecular profiling showed that nNOS blockade lowered the expression of chemical (SYN, SYP) and electrical (Cx36, Cx45) synaptic genes, disrupted their laminar distribution in vivo, and increased neurite length in primary retinal cultures without altering branching complexity. By combining ultrasensitive NO detection, large-scale electrophysiology, and mathematical network analysis, our results identify NO as a key regulator of circuit refinement that operates largely independently of the spatiotemporal dynamics of retinal waves during development. These findings reveal a molecular mechanism by which diffusible modulators shape neural networks independently of patterned activity and offer a framework for understanding how altered NO signaling might contribute to neurodevelopmental disorders characterized by impaired synaptic organization.
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Data
Datasets cited
- zenodo:20148989, at Zenodo; found in “Data availability”
Data availability
MEA recordings are available on https://
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
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Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 11 authors, 2 keywords, 3 funders, 43 references.
Cite
This paper
Walter, L. T., Móvio, M. I., Higa, G. S. V., Almeida, C. A. S. d., Raeisossadati, R., Borges, F. d. S., Ferraz, M. S. A., Cerchiaro, G., Schmeltzer, C., Rüdiger, S., & Kihara, A. H. (2026). Nitric oxide refines retinal circuit architecture independently of retinal wave dynamics. Cell death discovery, 12(1), 367. https://
BibTeX
@article{walter2026nitri
author = {Walter, Lais Takata and Móvio, Marília Inês and Higa, Guilherme Shigueto Vilar and Almeida, Cayo Antônio Soares de and Raeisossadati, Reza and Borges, Fernando da Silva and Ferraz, Mariana Sacrini Ayres and Cerchiaro, Giselle and Schmeltzer, Christian and Rüdiger, Sten and Kihara, Alexandre Hiroaki},
title = {{Nitric oxide refines retinal circuit architecture independently of retinal wave dynamics}},
journal = {Cell death discovery},
year = {2026},
month = jun,
volume = {12},
number = {1},
pages = {367},
publisher = {Nature Publishing Group},
issn = {2058-7716},
doi = {10.1038/
url = {https://
pmid = {42362501},
pmcid = {PMC13572502}
}
RIS
TY - JOUR
AU - Walter, Lais Takata
AU - Móvio, Marília Inês
AU - Higa, Guilherme Shigueto Vilar
AU - Almeida, Cayo Antônio Soares de
AU - Raeisossadati, Reza
AU - Borges, Fernando da Silva
AU - Ferraz, Mariana Sacrini Ayres
AU - Cerchiaro, Giselle
AU - Schmeltzer, Christian
AU - Rüdiger, Sten
AU - Kihara, Alexandre Hiroaki
TI - Nitric oxide refines retinal circuit architecture independently of retinal wave dynamics
T2 - Cell death discovery
J2 - Cell Death Discov
PY - 2026
DA - 2026/
VL - 12
IS - 1
SP - 367
SN - 2058-7716
PB - Nature Publishing Group
DO - 10.1038/
UR - https://
LA - en
ER -
CSL-JSON
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