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.

中文翻译：

---

系统整合期间的瞬时cAMP升高会增强远程上下文恐惧记忆。

记忆通过时间上的渐变过渡存储在我们的大脑中。随着时间的流逝，最近形成的存储器将转变为用于永久存储的远程存储器。多个大脑区域（例如海马和新皮层）参与了此过程。在这项研究中，我们旨在了解记忆系统整合的分子机制，并研究有助于这种调节的大脑区域。我们首先使用转基因小鼠品系进行了情景恐惧记忆测试，该小鼠品系在前脑区域表达外源性Aplysia octopamine受体，因此，响应章鱼胺治疗，​​环状单磷酸腺苷（cAMP）水平可能会暂时升高。从这个实验中 我们发现系统巩固期间前脑中cAMP水平的短暂升高导致远程恐惧记忆的增强，并在前扣带回皮质（ACC）的II / III层中增加了微型兴奋性突触电流。此外，使用腺相关病毒驱动的DREADD系统，我们研究了前脑中有助于记忆转移到长期关联的调节的特定区域。我们的结果表明，cAMP的瞬时升高在化学上是在ACC中诱导的，而不是在海马体中诱导的，并且表明远程记忆显着增强。这一发现表明，通过ACC中cAMP水平的升高，系统整合过程中的神经元激活有助于远程记忆的增强。