Gisquet-Verrier Pascale, Lynch Joseph F, Cutolo Pasquale, Toledano Daniel, Ulmen Adam, Jasnow Aaron M, Riccio David C
CNRS, University Paris-Sud, Neuroscience Paris-Saclay Institute (NeuroPSI), UMR 9197, F-91405 Orsay, France, and
Department of Psychological Sciences, Kent State University, Kent, Ohio 44242.
J Neurosci. 2015 Aug 19;35(33):11623-33. doi: 10.1523/JNEUROSCI.1386-15.2015.
Active (new and reactivated) memories are considered to be labile and sensitive to treatments disrupting the time-dependent consolidation/reconsolidation processes required for their stabilization. Active memories also allow the integration of new information for updating memories. Here, we investigate the possibility that, when active, the internal state provided by amnesic treatments is represented and integrated within the initial memory and that amnesia results from the absence of this state at testing. We showed in rats that the amnesia resulting from systemic, intracerebroventricular and intrahippocampal injections of the protein synthesis inhibitor cycloheximide, administered after inhibitory avoidance training or reactivation, can be reversed by a reminder, including re-administration of the same drug. Similar results were obtained with lithium chloride (LiCl), which does not affect protein synthesis, when delivered systemically after training or reactivation. However, LiCl can induce memory given that a conditioned taste aversion was obtained for a novel taste, presented just before conditioning or reactivation. These results indicate that memories can be established and maintained without de novo protein synthesis and that experimental amnesia may not result from a disruption of memory consolidation/reconsolidation. The findings more likely support the integration hypothesis: posttraining/postreactivation treatments induce an internal state, which becomes encoded with the memory, and should be present at the time of testing to ensure a successful retrieval. This integration concept includes most of the previous explanations of memory recovery after retrograde amnesia and critically challenges the traditional memory consolidation/reconsolidation hypothesis, providing a more dynamic and flexible view of memory.
This study provides evidence challenging the traditional consolidation/reconsolidation hypotheses that have dominated the literature over the past 50 years. Based on amnesia studies, that hypothesis states that active (i.e., new and reactivated) memories are similarly labile and (re)established in a time-dependent manner within the brain through processes that require de novo protein synthesis. Our data show that new/reactivated memories can be formed without protein synthesis and that amnesia can be induced by drugs that do not affect protein synthesis. We propose that amnesia results from memory integration of the internal state produced by the drug that is subsequently necessary for retrieval of the memory. This interpretation gives a dynamic view of memory, rapidly stored and easily updated when active.
活跃（新形成和重新激活）的记忆被认为是不稳定的，且对干扰其稳定所需的时间依赖性巩固/重新巩固过程的处理敏感。活跃的记忆还允许整合新信息以更新记忆。在此，我们研究一种可能性，即当记忆活跃时，失忆处理所产生的内部状态会在初始记忆中被表征并整合，且失忆是由于测试时缺乏这种状态所致。我们在大鼠中发现，在抑制性回避训练或重新激活后，通过全身、脑室内和海马内注射蛋白质合成抑制剂环己酰亚胺所导致的失忆，可通过提示（包括再次给予相同药物）而逆转。在训练或重新激活后全身给予不影响蛋白质合成的氯化锂（LiCl）时，也获得了类似结果。然而，鉴于在条件化或重新激活前呈现的一种新味道引发了条件性味觉厌恶，LiCl可诱导记忆形成。这些结果表明，记忆的建立和维持无需从头合成蛋白质，且实验性失忆可能并非由记忆巩固/重新巩固的破坏所致。这些发现更有可能支持整合假说：训练后/重新激活后的处理会诱导一种内部状态，该状态会与记忆一起被编码，且在测试时应存在以确保成功检索。这一整合概念涵盖了以往对逆行性失忆后记忆恢复的大多数解释，并对传统的记忆巩固/重新巩固假说提出了严峻挑战，为记忆提供了一个更具动态性和灵活性的观点。
本研究提供了证据，对过去50年主导文献的传统巩固/重新巩固假说提出了挑战。基于失忆研究，该假说指出活跃（即新形成和重新激活）的记忆同样不稳定，并通过需要从头合成蛋白质的过程在大脑中以时间依赖性方式（重新）建立。我们的数据表明，新的/重新激活的记忆可以在没有蛋白质合成的情况下形成，且失忆可由不影响蛋白质合成的药物诱导。我们提出，失忆是由药物产生的内部状态的记忆整合导致的，而这种状态随后是记忆检索所必需的。这种解释给出了一种记忆的动态观点，记忆在活跃时能快速存储且易于更新。
