Evidence that long-term potentiation occurs within individual hippocampal synapses during learning
Evidence that long-term potentiation occurs within individual hippocampal synapses during learning
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DOI：
10.1523/jneurosci.2003-07.2007
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发表时间：
2007-07-25
影响因子：
5.3
通讯作者：
Lynch, Gary
中科院分区：
文献类型：
--
作者：
Fedulov, Vadim;Rex, Christopher S.;Lynch, Gary
长时程增强（LTP）的稳定依赖于与肌动蛋白聚合相关的多个信号级联。我们使用其中之一，涉及调节蛋白cofilin的磷酸化，作为一个标志物，以测试是否LTP相关的变化发生在海马突触在无监督学习。在注射溶媒或NMDA受体拮抗剂（+/-）-3-（2-羧基哌嗪-4-基）丙基-1-膦酸（CPP）后，允许处理良好的大鼠探索区室化环境30分钟。另一组大鼠由溶剂注射、饲养笼对照组成。探索环境的溶剂处理大鼠在海马区CA 1中具有密集磷酸化（p）cofilin免疫反应性的棘比家庭笼组大鼠多30%。CPP消除了pCofilin阳性棘的增加和对所探索环境的记忆的行为证据。pCofilin和突触后密度蛋白95（PSD-95）的共免疫染色显示，pCofilin阳性棘上的突触比相邻（pCofilin阴性）棘上的突触大得多。这些结果表明，不寻常的细胞事件与LTP，包括突触大小的变化，发生在学习过程中的个别脊柱，并提供了一种技术映射潜在的痕迹。
Stabilization of long-term potentiation (LTP) depends on multiple signaling cascades linked to actin polymerization. We used one of these, involving phosphorylation of the regulatory protein cofilin, as a marker to test whether LTP-related changes occur in hippocampal synapses during unsupervised learning. Well handled rats were allowed to explore a compartmentalized environment for 30 min after an injection of vehicle or the NMDA receptor antagonist (+/-)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP). Another group of rats consisted of vehicle-injected, home-cage controls. Vehicle-treated rats that explored the environment had 30% more spines with dense phosphorylated (p) cofilin immunoreactivity in hippocampal field CA1 than did rats in the home-cage group. The increase in pCofilin-positive spines and behavioral evidence for memory of the explored environment were both eliminated by CPP. Coimmunostaining for pCofilin and the postsynaptic density protein 95 (PSD-95) showed that synapses on pCofilin-positive spines were substantially larger than those on neighboring (pCofilin-negative) spines. These results establish that uncommon cellular events associated with LTP, including changes in synapse size, occur in individual spines during learning, and provide a technique for mapping potential engrams.