Presynaptic SNAP25 supports maturation of hippocampal mossy fiber-CA3 synapses.

Overview

Authors: Shuichi Hayashi¹, Nobuhiko Ohno^2,3, Zoltán Molnár⁴, Kazunori Toida¹

ORCID iDs: Shuichi Hayashi, Nobuhiko Ohno, Zoltán Molnár, Kazunori Toida

Department of Anatomy, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan
Department of Anatomy, Division of Histology and Cell Biology, School of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan
Division of Ultrastructural Research, National Institute for Physiological Sciences, 5-1 Higashiyama Myodaiji, Okazaki, Aichi 444-8787, Japan
Department of Physiology, Anatomy and Genetics, Sherrington Building, University of Oxford, Parks Road, Oxford OX1 3PT, UK

Institutions: Kawasaki Medical School (Japan); Jichi Medical University (Japan); National Institute for Physiological Sciences (Japan); University of Oxford (United Kingdom)

Journal: iScience, volume 29, issue 7, article 116503

Dates: received 31 October 2025; accepted 5 June 2026; published online 20 June 2026

Type: Research article · Language: English

License: CC BY

Identifiers: DOI 10.1016/j.isci.2026.116503 · PMID 42383007 · PMCID PMC13315434 · OpenAlex W7165402879

Open access: gold, a free copy (OpenAlex)

Status: code on request

Categories: cellular / molecular (subfield)

Methods: Statistics, Evoked potentials

Keywords: molecular neuroscience, cellular neuroscience

Topic: Cellular transport and secretion (Cell Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex

Funding: Japan Society for the Promotion of Science (19K23786, 22K06242); Takeda Science Foundation; Ryobi Teien Memory Foundation; Wesco Science Foundation; Kawasaki Medical School; UK Medical Research Council (G00900901); St John’s Research Centre (21138077)

Citations: not cited yet (Europe PMC); 59 references in the paper

Research resources: guinea pig anti-VGLUT1 RRID:AB_2301751, RRID:AB_2340356, RRID:AB_2340462, RRID:AB_2340616, chicken anti-GFP RRID:AB_2534023, guinea pig anti-Bassoon RRID:AB_2924946, rabbit anti-HOMER1 RRID:AB_887730

Abstract

Mossy fiber (MF)-CA3 synapses in the hippocampus play vital roles in learning and memory. MFs have characteristic giant boutons with thorny excrescences on the dendrites of CA3 pyramidal neurons. The mechanisms underlying the development of this complex synaptic specialization remain unclear. In the present study, the loss of synaptosomal-associated protein 25 (SNAP25)—a protein essential for regulated synaptic vesicular release—increased the density but decreased the size of MF boutons and altered the postsynaptic distribution of homer scaffolding protein 1. Three-dimensional correlative light and electron microscopy revealed that although axon targeting and synapse formation were unaffected, excrescences failed to develop in MF boutons, resulting in a smaller contact area between MF boutons and CA3 dendrites. Moreover, SNAP25-deficient boutons displayed abnormal intracellular profiles, such as the accumulation of large synaptic vesicles. These findings indicate that presynaptic SNAP25 is essential for the maturation and maintenance of specialized hippocampal giant boutons.

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

Code

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• The data reported in this study are available from the lead contact upon request. • No original code was developed for the analysis. • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

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

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Version 2, 28 September 2026

Authors: added Shuichi Hayashi (0000-0001-7209-0007); Nobuhiko Ohno (0000-0002-6536-2753); Kazunori Toida (0000-0001-5421-1821); removed Shuichi Hayashi; Nobuhiko Ohno; Kazunori Toida

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 4 authors, 2 keywords, 7 funders, 58 references, 7 RRIDs.

Cite

This paper

Hayashi, S., Ohno, N., Molnár, Z., & Toida, K. (2026). Presynaptic SNAP25 supports maturation of hippocampal mossy fiber-CA3 synapses. iScience, 29(7), 116503. https://doi.org/10.1016/j.isci.2026.116503

BibTeX

@article{hayashi2026presynaptic, author = {Hayashi, Shuichi and Ohno, Nobuhiko and Molnár, Zoltán and Toida, Kazunori}, title = {{Presynaptic SNAP25 supports maturation of hippocampal mossy fiber-CA3 synapses}}, journal = {iScience}, year = {2026}, month = jun, volume = {29}, number = {7}, pages = {116503}, publisher = {Elsevier}, issn = {2589-0042}, doi = {10.1016/j.isci.2026.116503}, url = {https://doi.org/10.1016/j.isci.2026.116503}, pmid = {42383007}, pmcid = {PMC13315434} }

RIS

TY - JOUR AU - Hayashi, Shuichi AU - Ohno, Nobuhiko AU - Molnár, Zoltán AU - Toida, Kazunori TI - Presynaptic SNAP25 supports maturation of hippocampal mossy fiber-CA3 synapses T2 - iScience J2 - iScience PY - 2026 DA - 2026/06/20 VL - 29 IS - 7 SP - 116503 SN - 2589-0042 PB - Elsevier DO - 10.1016/j.isci.2026.116503 UR - https://doi.org/10.1016/j.isci.2026.116503 LA - en ER -

CSL-JSON

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