Plasticity of Long-Term Plasticity of a Single Sensorimotor Synapse

神经生物学中最重要的问题之一是记忆是如何在大脑中保持数十年的。传统上，人们一直认为，经过诱导和最初的巩固阶段，记忆是相对持久的，对干扰具有抵抗力。然而，最近的证据表明，长期记忆远比之前认为的更不稳定。长期记忆不稳定的证据来自一项研究，在这些研究中，动物的巩固记忆被重新激活，通常是通过给动物一种刺激，让它想起最初的学习经历。已经发现，重新激活会使储存的长期记忆受到干扰，例如抑制蛋白质合成，从而破坏新形成的记忆。这一发现导致了一种观点，即在重新激活后，长期记忆经历了一个新的巩固阶段(“重新巩固”)，在这个过程中，它们是脆弱的，容易被消除。虽然巩固的记忆在重新激活后经历重新巩固的概念越来越被神经生物学家接受，但记忆重新巩固的机制却鲜为人知。这个项目将使用一个简单的无脊椎动物有机体来获得对调节记忆重新巩固的细胞和分子过程的一般见解。这个模型系统的一个显著优点是，在分离的细胞培养中，可以在单个感觉运动突触的水平上检查记忆的再巩固。这使得对再整合进行严格的机械分析成为可能。在该项目期间将解决的问题包括：记忆重新巩固的中断在多大程度上实际上消除了记忆；参与原始记忆巩固的分子信号过程与涉及记忆重新巩固的分子信号过程之间的相似性；以及重新巩固对记忆强度的影响。后一个问题将从行为和突触两个层面进行研究。该项目的更广泛影响包括培训任职人数不足的研究生和本科生。此外，还将开展大量的公众宣传活动。

One of the most important problems in neurobiology is how memories are maintained in the brain over the course of decades. Traditionally, it has been thought that, after induction and an initial period of consolidation, memories are relatively permanent and resistant to disruption. Recent evidence, however, indicates that long-term memories are far more labile than previously supposed. Evidence for the lability of long-term memory has come from studies in which a consolidated memory is reactivated in an animal, typically by giving the animal a stimulus that reminds it of the original learning experience. It has been found that reactivation renders a stored, long-term memory subject to disruption by manipulations, such as inhibition of protein synthesis, that disrupt newly formed memories. This finding has led to the idea that, upon reactivation, long-term memories undergo a new episode of consolidation ("reconsolidation"), during which they are fragile and subject to elimination. Although the notion that consolidated memories undergo reconsolidation following their reactivation is increasingly accepted by neurobiologists, the mechanisms of memory reconsolidation are poorly understood. This project will use a simple invertebrate organism to gain general insights into the cellular and molecular processes that mediate memory reconsolidation. A significant advantage of this model system is that memory reconsolidation can be examined at the level of a single sensorimotor synapse in dissociated cell culture. This permits rigorous mechanistic analyses of reconsolidation. Among the questions that will be addressed during the project are the extent to which disruption of reconsolidation of a memory actually eliminates the memory; the similarity between the molecular signaling processes that are involved in original memory consolidation to those involved in memory reconsolidation; and the effect of reconsolidation on the strength of the memory. The latter question will be examined on both the behavioral and synaptic levels. The broader impacts of this project include the training of underrepresented graduate students and undergraduates. In addition, significant public outreach will be undertaken.