Ageta-Ishihara N., Fukazawa Y., Arima-Yoshida F., Okuno H., Ishii Y., Takao K., Konno K., Fujishima K., Ageta H., Hioki H., Tsuchida K., Sato Y., Kengaku M., Watanabe M., Watabe A.M., Manabe T., Miyak2025 · 記述言語: 英語 掲載種別: 研究論文(学術雑誌) 出版者・発行元: Cell Reports 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 Ca2+ 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. DOI: 10.1016/j.celrep.2025.115352 Scopus PubMed researchmap
Wagatsuma N., Terada Y., Okuno H., Ageta-Ishihara N. . Local connections among excitatory neurons underlie characteristics of enriched environment exposure-induced neuronal response modulation2025 · 担当区分: 筆頭著者, 最終著者, 責任著者 記述言語: 日本語 出版者・発行元: Frontiers in Systems Neuroscience Environmental enrichment, an enhancement in the breeding environment of laboratory animals, enhance development of the cortical circuit and suppresses brain dysfunction. We quantitatively investigated the influences of enriched environment (EE) exposure, on responses in layers 2/3 (L2/3) of the primary visual area (V1) of mice. EE modifies visual cortex plasticity by inducing immediate early genes. To detect this, we performed immunostaining for the immediate early gene product c-Fos. EE exposure significantly increased the number of neurons with high c-Fos fluorescence intensity compared with those of mice under standard housing (SH). In contrast, there was no significant difference in the number of neurons exhibiting low c-Fos intensity between the SH and EE exposure groups. To further investigate the mechanism of modulation by EE exposure, we developed a microcircuit model with a biologically plausible L2/3 of V1 that combined excitatory pyramidal (Pyr) neurons and three inhibitory interneuron subclasses. In the model, synaptic strengths between Pyr neurons were determined according to a log-normal distribution. Model simulations with various inputs mimicking physiological conditions for SH and EE exposure quantitatively reproduced the experimentally observed activity modulation induced by EE exposure. These results suggested that synaptic connections among Pyr neurons obeying a log-normal distribution underlie the characteristic EE-exposure-induced modulation of L2/3 in V1. DOI: 10.3389/fnsys.2025.1525717 Scopus PubMed
Kazuki Ito, Keiichiro Sato, Yousuke Tsuneoka, Takashi Maejima, Hiroyuki Okuno, Yumi Hamasaki, Shunsaku Murakawa, Yuzu Takabayashi, Chihiro Yoshihara, Sayaka Shindo, Haruka Uki, Stefan Herlitze, Masahi2023 · 出版者・発行元: Cold Spring Harbor Laboratory Summary A dramatic shift from aggressive infanticidal to paternal behaviors is an essential event for male mice after mating. While the central part of the medial preoptic area (cMPOA) has been shown to critically mediate the paternal behaviors in mice, how this brain region becomes activated by mating and subsequent interaction with pups has not been investigated. Here, we demonstrate that the reduction in inhibitory synaptic strength towards the cMPOA provided by posterior-dorsal medial amygdala (MePD) neurons is a key event for the post-mating behavioral shift in males. Consistent with this, we found optogenetic disinhibition of Me<sup>Cartpt</sup>to the cMPOA synapses reduces male aggression towards pups. The cMPOA of paternal mice mediated pup-induced neural plastic changes in the bed nucleus of the stria terminalis. These findings provide possible functions of cMPOA neural circuits required for the reception to young in male mice. DOI: 10.1101/2023.10.23.560098 researchmap