Septin 3 regulates memory and L-LTP-dependent extension of endoplasmic reticulum into spines
Transient memories are converted to persistent memories at the synapse and circuit/systems levels. The synapse-level consolidation parallels electrophysiological transition from early- to late-phase long-term potentiation of synaptic transmission (E-/L-LTP). While glutamate signaling upregulations coupled with dendritic spine enlargement are common underpinnings of E-LTP and L-LTP, synaptic mechanisms conferring persistence on L-LTP remain unclear. Here, we show that L-LTP induced at the perforant path-hippocampal dentate gyrus (DG) synapses accompanies cytoskeletal remodeling that involves actin and the septin subunit SEPT3. L-LTP in DG neurons causes fast spine enlargement, followed by SEPT3-dependent smooth endoplasmic reticulum (sER) extension into enlarged spines. Spines containing sER show greater Ca<sup>2+</sup> responses upon synaptic input and local synaptic activity. Consistently, Sept3 knockout in mice (Sept3<sup>-/-</sup>) impairs memory consolidation and causes a scarcity of sER-containing spines. These findings indicate a concept that sER extension into active spines serves as a synaptic basis of memory consolidation.
Authors
- Kazuto Fujishima (ORCID: https://orcid.org/0000-0001-6374-4486)
- Fumiko Arima‐Yoshida
- Makoto Kinoshita (ORCID: https://orcid.org/0000-0002-7592-2400)
- Yoshikatsu Sato (ORCID: https://orcid.org/0000-0002-4967-2698)
- Ayako M. Watabe (ORCID: https://orcid.org/0000-0002-6916-5757)
- Toshiya Manabe (ORCID: https://orcid.org/0000-0002-5359-6704)
- Natsumi Ageta‐Ishihara (ORCID: https://orcid.org/0000-0003-2543-4828)
- Hiroshi Ageta
- Mineko Kengaku (ORCID: https://orcid.org/0000-0002-1666-3648)
- Kohtarou Konno (ORCID: https://orcid.org/0000-0003-4964-8011)
- Kunihiro Tsuchida (ORCID: https://orcid.org/0000-0002-3983-5756)
- Haruhiko Bito (ORCID: https://orcid.org/0000-0001-6315-9594)
- Keizo Takao (ORCID: https://orcid.org/0000-0002-4734-3583)
- Hiroyuki Hioki (ORCID: https://orcid.org/0000-0002-0152-7854)
- Kaoru Inokuchi (ORCID: https://orcid.org/0000-0002-5393-3133)
- Yugo Fukazawa (ORCID: https://orcid.org/0000-0001-7436-8797)
- Tsuyoshi Miyakawa (ORCID: https://orcid.org/0000-0003-0137-8200)
- Hiroyuki Okuno (ORCID: https://orcid.org/0000-0001-6237-6503)
- Yuichiro Ishii (ORCID: https://orcid.org/0000-0002-3059-997X)
- Masahiko Watanabe (ORCID: https://orcid.org/0000-0002-5262-6799)
Institutions
- Kagoshima University (JP)
- University of Fukui (JP)
- Jikei University School of Medicine (JP)
- Toho University (JP)
- Fujita Health University (JP)
- Hokkaido University (JP)
- Kyoto University (JP)
- Juntendo University (JP)
- Jikei University Kashiwa hospital (JP)
- University of Toyama (JP)
- Nagoya University (JP)
- The University of Tokyo (JP)
- Osaka University of Pharmaceutical Sciences (JP)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-02-28
- DOI
- https://doi.org/10.1016/j.celrep.2025.115352
- Citations
- 12
- Primary Topic
- Mitochondrial Function and Pathology
- Type
- article
- Field-Weighted Citation Impact
- 8.87