Department of Psychiatry, School of Medicine, Uniformed Services University, Bethesda, MD, 20814, USA.
Brain Topogr. 2013 Jul;26(3):468-78. doi: 10.1007/s10548-012-0266-6. Epub 2013 Jan 16.
A key question in neuroscience is how memory is selectively allocated to neural networks in the brain. This question remains a significant research challenge, in both rodent models and humans alike, because of the inherent difficulty in tracking and deciphering large, highly dimensional neuronal ensembles that support memory (i.e., the engram). In a previous study we showed that consolidation of a new fear memory is allocated to a common topography of amygdala neurons. When a consolidated memory is retrieved, it may enter a labile state, requiring reconsolidation for it to persist. What is not known is whether the original spatial allocation of a consolidated memory changes during reconsolidation. Knowledge about the spatial allocation of a memory, during consolidation and reconsolidation, provides fundamental insight into its core physical structure (i.e., the engram). Using design-based stereology, we operationally define reconsolidation by showing a nearly identical quantity of neurons in the dorsolateral amygdala (LAd) that expressed a plasticity-related protein, phosphorylated mitogen-activated protein kinase, following both memory acquisition and retrieval. Next, we confirm that Pavlovian fear conditioning recruits a stable, topographically organized population of activated neurons in the LAd. When the stored fear memory was briefly reactivated in the presence of the relevant conditioned stimulus, a similar topography of activated neurons was uncovered. In addition, we found evidence for activated neurons allocated to new regions of the LAd. These findings provide the first insight into the spatial allocation of a fear engram in the LAd, during its consolidation and reconsolidation phase.
神经科学中的一个关键问题是记忆如何选择性地分配到大脑中的神经网络。这个问题仍然是一个重大的研究挑战，无论是在啮齿动物模型还是人类中，因为跟踪和破译支持记忆（即记忆痕迹）的大型、高维神经元集合具有内在的困难。在之前的一项研究中，我们表明新的恐惧记忆的巩固被分配到杏仁核神经元的共同拓扑结构中。当巩固的记忆被检索时，它可能进入不稳定状态，需要重新巩固才能使其持续存在。目前尚不清楚在重新巩固过程中，巩固记忆的原始空间分配是否会发生变化。关于记忆在巩固和重新巩固期间的空间分配的知识，为其核心物理结构（即记忆痕迹）提供了基本的见解。我们通过显示在记忆获得和检索后，表达一种与可塑性相关的蛋白质、磷酸化丝裂原活化蛋白激酶的背外侧杏仁核（LAd）中的神经元数量几乎相同，从而操作定义重新巩固。接下来，我们证实了条件性恐惧反应会招募 LAd 中稳定的、具有拓扑结构的激活神经元群体。当存储的恐惧记忆在相关条件刺激存在下短暂重新激活时，会发现类似的激活神经元拓扑。此外，我们还发现了证据表明激活的神经元被分配到 LAd 的新区域。这些发现为在 LAd 中巩固和重新巩固阶段恐惧记忆痕迹的空间分配提供了第一个见解。
