Ageta-Ishihara Natsumi, Fukazawa Yugo, Arima-Yoshida Fumiko, Okuno Hiroyuki, Ishii Yuichiro, Takao Keizo, Konno Kohtarou, Fujishima Kazuto, Ageta Hiroshi, Hioki Hiroyuki, Tsuchida Kunihiro, Sato Yoshikatsu, Kengaku Mineko, Watanabe Masahiko, Watabe Ayako M, Manabe Toshiya, Miyakawa Tsuyoshi, Inokuchi Kaoru, Bito Haruhiko, Kinoshita Makoto
Department of Biomolecular Science, Faculty of Science, Toho University, Funabashi, Chiba 274-8510, Japan; Department of Molecular Biology, Division of Biological Sciences, Nagoya University Graduate School of Science, Chikusa-ku, Nagoya 464-8602, Japan.
Division of Brain Structure and Function, Faculty of Medical Science, University of Fukui, Yoshida-gun, Fukui 910-1193, Japan.
Cell Rep. 2025 Mar 25;44(3):115352. doi: 10.1016/j.celrep.2025.115352. Epub 2025 Feb 28.
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 responses upon synaptic input and local synaptic activity. Consistently, Sept3 knockout in mice (Sept3) 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.
短暂记忆在突触以及神经回路/系统水平上转化为持久记忆。突触水平的巩固与突触传递从早期到晚期长时程增强（E-LTP/L-LTP）的电生理转变相似。虽然谷氨酸信号上调以及树突棘增大是E-LTP和L-LTP的共同基础，但赋予L-LTP持久性的突触机制仍不清楚。在这里，我们表明，在穿通通路-海马齿状回（DG）突触处诱导的L-LTP伴随着涉及肌动蛋白和septin亚基SEPT3的细胞骨架重塑。DG神经元中的L-LTP导致树突棘快速增大，随后SEPT3依赖的滑面内质网（sER）延伸至增大的树突棘中。含有sER的树突棘在突触输入和局部突触活动时表现出更大的钙反应。同样，小鼠中的Sept3基因敲除（Sept3-/-）会损害记忆巩固，并导致含有sER的树突棘数量减少。这些发现表明了一个概念，即sER延伸至活跃的树突棘中是记忆巩固的突触基础。
