小柯机器人

美国德州农工大学Stephen Maren研究小组实现对海马依赖性恐惧记忆的捕获和削弱。2021年4月1日，国际知名学术期刊《自然—神经科学》在线发表了这一成果。

研究人员使用了向后（BW）调节程序来间接检索和操纵雄性大鼠的海马（HPC）依赖性关联恐惧印记。研究人员发现，对BW条件刺激（CS）的条件性僵化是通过对条件关联的恐惧来介导的，可以激活HPC群体（这能够被捕捉到并通过化学方法激活来驱动恐惧），并且受到检索后蛋白质合成抑制的损害。

这些结果表明，间接检索的关联恐惧记忆会重新激活HPC集成体，并进行依赖蛋白质合成的重组。依靠间接获取创伤性记忆（例如想象中的暴露）的临床干预措施可能会打开一个新的治疗窗口，用于编辑或消除驱动病理恐惧的神经表征。 

据了解，记忆再巩固可能是抑制病理性恐惧记忆的可行治疗靶标。在临床中，偶然或虚构的提醒被用于安全地检索在其他地方发生的经历的创伤性记忆。但是，间接检索的创伤记忆是否对破坏敏感尚不清楚。

附：英文原文

Title: Covert capture and attenuation of a hippocampus-dependent fear memory

Author: Reed L. Ressler, Travis D. Goode, Sohmee Kim, Karthik R. Ramanathan, Stephen Maren

Issue&Volume: 2021-04-01

Abstract: Reconsolidation may be a viable therapeutic target to inhibit pathological fear memories. In the clinic, incidental or imaginal reminders are used for safe retrieval of traumatic memories of experiences that occurred elsewhere. However, it is unknown whether indirectly retrieved traumatic memories are sensitive to disruption. Here we used a backward (BW) conditioning procedure to indirectly retrieve and manipulate a hippocampus (HPC)-dependent contextual fear engram in male rats. We show that conditioned freezing to a BW conditioned stimulus (CS) is mediated by fear to the conditioning context, activates HPC ensembles that can be covertly captured and chemogenetically activated to drive fear, and is impaired by post-retrieval protein synthesis inhibition. These results reveal that indirectly retrieved contextual fear memories reactivate HPC ensembles and undergo protein synthesis-dependent reconsolidation. Clinical interventions that rely on indirect retrieval of traumatic memories, such as imaginal exposure, may open a window for editing or erasure of neural representations that drive pathological fear. This study shows that hippocampus-dependent fear memories can be indirectly reactivated, captured and pharmacologically attenuated in rats. This reinforces the utility of imaginal reminders to target traumatic memories in humans.

DOI: 10.1038/s41593-021-00825-5

Source: https://www.nature.com/articles/s41593-021-00825-5

Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex