The Developing Engram – Imaging Memory Consolidation in Wakefulness and Sleep

一个几十年来一直激励着研究的问题是，持续的感知是如何转化为持久的记忆的。新的经历会在我们的大脑中留下持久的印记，即所谓的“记忆印记”。但是，是什么决定了一个事件是否会产生神经印记，以及这种过去的身体记录会持续多久？只有我们能够观察和操纵大脑中记忆痕迹的形成和发展，才能令人满意地回答这些问题。在编码之后，新的记忆必须被转化为长期使用的存储。在这个巩固过程中，支持新记忆的神经基质应该逐渐从高度可塑的海马体转移到学习速度较慢的新皮层区域，这一过程被称为系统记忆巩固。这种转变被认为是通过反复训练新皮层记忆网络来实现的，要么是通过主动排练，要么是通过睡眠中的离线再激活。直到最近，研究支持记忆巩固的隐蔽过程一直很困难。新的成像方法和分析方法的出现，使得定位和跟踪动物和人类的记忆印痕成为可能。长期以来，人们一直认为大脑新皮层是一个缓慢的学习者，但应用这些工具的研究发现，独立的大脑新皮层记忆印痕从学习开始就迅速形成。这一建议的总体目标是探索我们认为有助于从海马体到新皮层的物理记忆痕迹加速重新分配的三个因素-检索，分布式练习和睡眠。我们将应用新的扩散加权成像的学习诱导可塑性在人类大脑测试如何和在哪里存储的记忆，并观察他们的重新分配随着时间的推移。特别是，我们将(1)评估新皮层印痕在重复排练中出现的速度，以及它们是否在相对于海马体印痕的时间延迟中形成；(2)测试快速形成的新皮层印痕是否已经携带了有关先前学习经验的特定信息；(3)确定睡眠期间的记忆再激活是否促进了新皮层的可塑性。(4)测试学习和分布式实践学习等学习策略的有益效果是否可以归因于系统整合的加速。我们的研究结果有助于批判性地修正记忆巩固模型，这样他们就能更准确地预测新皮层是如何促进记忆处理的。大脑皮层的储存对于新记忆的长期保持至关重要。因此，阐明促进系统巩固和新皮层可塑性的因素不仅对基础研究，而且对临床和教育环境都具有最大的相关性。

A question that has motivated research for decades is how continuous perception is transformed into lasting memories. New experiences leave lasting imprints in our brain, so-called “memory engrams.” But what determines whether an event will engender a neural engram and how long this physical record of the past will endure? Only if we can observe and manipulate the formation and development of memory traces in the brain can these questions be satisfactorily answered.After encoding, new memories have to be transformed to be stored for long term usage. During the course of this consolidation, the neural substrate supporting new memories is supposed to gradually shift from highly plastic hippocampal to slower-learning neocortical regions, a process that has been termed systems memory consolidation. This transformation is thought to be achieved by repeated training of neocortical memory networks, either by active rehearsal or by offline reactivation during sleep.Until recently, it has been difficult to study the covert processes that support memory consolidation. The advent of novel imaging methods and analysis approaches has now made it possible to locate and track memory engrams in both animals and humans. Contrary to the long-held belief that the neocortex is a slow learner, studies applying these tools have found that independent neocortical memory engrams are formed rapidly from the outset of learning.The overall goal of this proposal is to explore three factors that we think contribute to an accelerated redistribution of physical memory traces from the hippocampus to neocortex –retrieval, distributed practice, and sleep. We will apply novel diffusion-weighted imaging of learning induced plasticity in the human brain to test how and where memories are stored in the brain and to observe their redistribution over time. In particular, we will (1) assess how fast neocortical engrams emerge over repeated rehearsal, and whether they are formed at a temporal delay with respect to the hippocampal engram, (2) test whether rapidly formed neocortical engrams already carry specific information about the previous learning experience, (3) determine whether memory reactivation during sleep facilitates plasticity in the neocortex, and (4) whether beneficial effects of learning strategies such as learning by testing and distributed practice can be attributed to an acceleration of systems consolidation.Our results can help to critically revise model of memory consolidation, such that they make more accurate predictions about how the neocortex contributes to memory processing. Neocortical storage is critical for the long-term retention of new memories. Elucidating the factors that facilitate systems consolidation and neocortical plasticity is thus of the greatest relevance, not only for basic research, but also for clinical and educational settings.