Interdisciplinary Program in Neuroscience, Seoul National University, 1 Gwanangno, Gwanak-gu, Seoul 08826, Republic of Korea; Neurobiology Laboratory, Department of Biological Sciences, College of Natural Sciences, Seoul National University, Gwanangno 599, Gwanak-Gu, Seoul 08826, Republic of Korea.
Neurobiology Laboratory, Department of Biological Sciences, College of Natural Sciences, Seoul National University, Gwanangno 599, Gwanak-Gu, Seoul 08826, Republic of Korea.
Neurobiol Learn Mem. 2020 Mar;169:107171. doi: 10.1016/j.nlm.2020.107171. Epub 2020 Jan 21.
Memory is stored in our brains over a temporally graded transition. With time, recently formed memories are transformed into remote memories for permanent storage; multiple brain regions, such as the hippocampus and neocortex, participate in this process. In this study, we aimed to understand the molecular mechanism of systems consolidation of memory and to investigate the brain regions that contribute to this regulation. We first carried out a contextual fear memory test using a transgenic mouse line, which expressed exogenously-derived Aplysia octopamine receptors in the forebrain region, such that, in response to octopamine treatment, cyclic adenosine monophosphate (cAMP) levels could be transiently elevated. From this experiment, we revealed that transient elevation of cAMP levels in the forebrain during systems consolidation led to an enhancement in remote fear memory and increased miniature excitatory synaptic currents in layer II/III of the anterior cingulate cortex (ACC). Furthermore, using an adeno-associated-virus-driven DREADD system, we investigated the specific regions in the forebrain that contribute to the regulation of memory transfer into long-term associations. Our results implied that transient elevation of cAMP levels was induced chemogenetically in the ACC, but not in the hippocampus, and showed a significant enhancement of remote memory. This finding suggests that neuronal activation during systems consolidation through the elevation of cAMP levels in the ACC contributes to remote memory enhancement.
记忆是在时间梯度上在我们的大脑中存储的。随着时间的推移，最近形成的记忆被转化为远程记忆，以便永久存储；多个脑区，如海马体和新皮层，参与了这个过程。在这项研究中，我们旨在了解记忆的系统巩固的分子机制，并研究对这一调节有贡献的脑区。我们首先使用一种转基因小鼠系进行了情境性恐惧记忆测试，该小鼠系在前脑区域表达了外源衍生的海兔章鱼胺受体，使得在对章鱼胺处理的反应中，环腺苷单磷酸（cAMP）水平可以短暂升高。从这个实验中，我们揭示了在系统巩固过程中，前脑区 cAMP 水平的短暂升高导致远程恐惧记忆增强，并在前扣带皮层（ACC）的 II/III 层中增加了微小兴奋性突触电流。此外，我们使用腺相关病毒驱动的 DREADD 系统，研究了前脑区中特定的区域对记忆转移到长期关联的调节作用。我们的结果表明，cAMP 水平在 ACC 中的化学遗传诱导短暂升高，但在海马体中没有，并且远程记忆显著增强。这一发现表明，通过在 ACC 中升高 cAMP 水平，神经元在系统巩固过程中的激活有助于远程记忆增强。
