Traceable stimulus-dependent rapid molecular changes in dendritic spines in the brain
Traceable stimulus-dependent rapid molecular changes in dendritic spines in the brain
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大脑树突棘中可追踪的刺激依赖性快速分子变化
DOI：
10.1038/s41598-020-72248-4
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发表时间：
2020
影响因子：
4.6
通讯作者：
Yamada Maki K.
中科院分区：
文献类型：
--
作者：
Kuboyama Kazuya;Inoue Takafumi;Hashimotodani Yuki;Itoh Takuya;Suzuki Tohsuke;Tetsuzawa Aya;Ohtsuka Yosuke;Kinoshita Ryo;Takara Ren;Miyazawa Tohru;Gusain Pooja;Kano Masanobu;Yamada Maki K.
树突棘的功能是微室，可以改变其相关突触的效率。在这里，我们分析了刺激依赖的脊柱分子变化。f -肌动蛋白封盖蛋白CapZ在树突棘的部分区域内积累，这些区域已经诱导了长期增强。我们制作了一种转基因小鼠系AiCE-Tg，其中表达了带有增强绿色荧光蛋白（EGFP-CapZ）标记的CapZ。在AiCE-Tg小鼠单侧视觉或体感觉刺激20分钟后，在刺激侧皮层的树突棘亚群中选择性地观察到相对的EGFP-CapZ信号增强；这种左右差异被NMDA受体阻断所消除。α-肌动蛋白是一种可以募集AMPA受体的PSD-95结合蛋白，免疫标记表明，α-肌动蛋白信号在EGFP-CapZ信号最亮的棘（前100）中比在EGFP-CapZ信号更典型的棘（前1000）中更频繁地共定位。这种刺激依赖性的EGFP-CapZ在体内的重新分布代表了一种具有可塑性特征的新分子事件，并且在AiCE-Tg小鼠中明亮的EGFP-CapZ使高capz棘在体内和离体中可追溯。该小鼠品系有潜力用于揭示序列分子事件，包括突触标记，并将这些脊柱中的多种类型的可塑性联系起来，扩展与记忆机制相关的知识。
Dendritic spines function as microcompartments that can modify the efficiency of their associated synapses. Here, we analyzed stimulus-dependent molecular changes in spines. The F-actin capping protein CapZ accumulates in parts of dendritic spines within regions where long-term potentiation has been induced. We produced a transgenic mouse line, AiCE-Tg, in which CapZ tagged with enhanced green fluorescence protein (EGFP-CapZ) is expressed. Twenty minutes after unilateral visual or somatosensory stimulation in AiCE-Tg mice, relative EGFP-CapZ signal intensification was seen in a subset of dendritic spines selectively in stimulated-side cortices; this right-left difference was abolished by NMDA receptor blockade. Immunolabeling of α-actinin, a PSD-95 binding protein that can recruit AMPA receptors, showed that the α-actinin signals colocalized more frequently in spines with the brightest EGFP-CapZ signals (top 100) than in spines with more typical EGFP-CapZ signal strength (top 1,000). This stimulus-dependent in vivo redistribution of EGFP-CapZ represents a novel molecular event with plasticity-like characteristics, and bright EGFP-CapZ in AiCE-Tg mice make high-CapZ spines traceable in vivo and ex vivo. This mouse line has the potential to be used to reveal sequential molecular events, including synaptic tagging, and to relate multiple types of plasticity in these spines, extending knowledge related to memory mechanisms.
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影响因子：
3.7
作者：
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通讯作者：
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16.2
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通讯作者：
M. Stryker