Interfering with the Actin Network and Its Effect on Long-Term Potentiation and Synaptic Tagging in Hippocampal CA1 Neurons in Slices In Vitro
Interfering with the Actin Network and Its Effect on Long-Term Potentiation and Synaptic Tagging in Hippocampal CA1 Neurons in Slices In Vitro
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DOI：
10.1523/jneurosci.2045-09.2009
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发表时间：
2009-09-30
影响因子：
5.3
通讯作者：
Frey, Julietta U.
中科院分区：
文献类型：
--
作者：
Ramachandran, Binu;Frey, Julietta U.
长时程增强（LTP）是记忆形成的一种细胞相关物，它需要肌动蛋白细胞骨架的动态变化。正如其他人所表明的，肌动蛋白网络的聚合对于LTP的早期阶段很重要。在此，我们研究了肌动蛋白动力学在突触标记中的作用，特别是在体外海马脑片CA1区诱导蛋白质合成依赖的晚期LTP中的作用。我们发现抑制肌动蛋白聚合会影响不依赖蛋白质合成的早期LTP，阻止晚期LTP，并干扰海马CA1顶树突的突触标记。应用结构不同的肌动蛋白聚合抑制剂拉特伦库林A或细胞松弛素D可阻断早期LTP向晚期LTP的转化。我们认为，肌动蛋白网络是诱导和维持早期LTP的早期“内务处理”过程所必需的。此外，抑制肌动蛋白动力学会对突触标记复合物的形成产生负面作用。我们提出肌动蛋白是CA1顶树突中另一种特定于标记的分子，它直接参与标记/捕获机制。因此，抑制肌动蛋白网络会阻止标记复合物与可塑性相关蛋白的相互作用。这导致在LTP诱导过程中通过抑制肌动蛋白网络来阻止晚期LTP的形成。
Long-term potentiation (LTP) is a cellular correlate for memory formation, which requires the dynamic changes of the actin cytoskeleton. As shown by others, the polymerization of the actin network is important for early stages of LTP. Here, we investigated the role of actin dynamics in synaptic tagging and particularly in the induction of protein synthesis-dependent late-LTP in the CA1 region in hippocampal slices in vitro. We found that the inhibition of actin polymerization affects protein synthesis-independent early-LTP, prevents late-LTP, and interferes with synaptic tagging in apical dendrites of hippocampal CA1. The transformation of early-LTP into late-LTP was blocked by the application of the structurally different actin polymerization inhibitors latrunculin A or cytochalasin D. We suggest that the actin network is required for early "housekeeping" processes to induce and maintain early-LTP. Furthermore, inhibition of actin dynamics negatively interacts with the setting of the synaptic tagging complex. We propose actin as a further tag-specific molecule in apical CA1 dendrites where it is directly involved in the tagging/capturing machinery. Consequently, inhibition of the actin network prevents the interaction of tagging complexes with plasticity-related proteins. This results in the prevention of late-LTP by inhibition of the actin network during LTP induction.