Distinct roles of hippocampal de novo protein synthesis and actin rearrangement in extinction of contextual fear
Distinct roles of hippocampal de novo protein synthesis and actin rearrangement in extinction of contextual fear
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DOI：
10.1523/jneurosci.5112-03.2004
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发表时间：
2004-02-25
影响因子：
5.3
通讯作者：
Radulovic, J
中科院分区：
文献类型：
--
作者：
Fischer, A;Sananbenesi, F;Radulovic, J
据信，从头蛋白质合成从根本上与涉及条件反应的获得和消退的神经元回路中的突触变化有关。最近的研究表明，神经元的可塑性也可能改变细胞骨架重排独立的蛋白质合成。我们研究了这些过程在海马中的作用，在获得和消退的上下文依赖性条件性恐惧小鼠。海马内注射蛋白质合成抑制剂茴香霉素和嘌呤霉素，或肌动蛋白重排抑制剂细胞松弛素D和latrunculin A，防止收购的上下文依赖性恐惧。出乎意料的是，茴香霉素和嘌呤霉素增强了灭绝，而没有消除恐惧记忆。相比之下，细胞松弛素D和latrunculin A阻止灭绝的上下文依赖性冻结。在这些研究结果的基础上，有人建议，某些海马机制介导的条件性背景恐惧的消退抑制蛋白质合成，涉及肌动蛋白重排。这种机制可能主要会引起储存条件记忆的海马回路的修改。
It is believed that de novo protein synthesis is fundamentally linked to synaptic changes in neuronal circuits involved in acquisition and extinction of conditioned responses. Recent studies show that neuronal plasticity may be also altered by cytoskeletal rearrangement independently of protein synthesis. We investigated the role of these processes in the hippocampus during acquisition and extinction of context-dependent conditioned fear in mice. Intrahippocampal injections of the protein synthesis inhibitors anisomycin and puromycin, or of the actin rearrangement inhibitors cytochalasin D and latrunculin A, prevented the acquisition of context-dependent fear. Unexpectedly, anisomycin and puromycin enhanced extinction without erasing the fear memory. In contrast, cytochalasin D and latrunculin A prevented extinction of context-dependent freezing. On the basis of these findings, it is suggested that certain hippocampal mechanisms mediating extinction of conditioned contextual fear are inhibited by protein synthesis and involve actin rearrangement. Such mechanisms might predominantly elicit modifications of hippocampal circuits that store the conditioning memory.