Erasing traumatic memory during memory reconsolidation is a promising retrieval-extinction strategy for post-traumatic stress disorder (PTSD). Here, we developed an acute social defeat stress (SDS) mouse model with short-term and re-exposure-evoked long-term social avoidance. SDS-associated traumatic memories were identified to be stored in basolateral amygdala (BLA) engram cells. A single intraperitoneal administration of subanesthetic-dose ketamine within, but not beyond, the re-exposure time window significantly alleviates SDS-induced social avoidance, which reduces the activity and quantity of reactivated BLA engram cells. Furthermore, activation or inhibition of dopaminergic projections from the ventral tegmental area to the BLA effectively mimics or blocks the therapeutic effect of re-exposure with ketamine and is dopamine D2 receptor dependent. Single-cell RNA sequencing reveals that re-exposure with ketamine triggered significant changes in memory-related pathways in the BLA. Together, our research advances the understanding of how ketamine mitigates PTSD symptoms and offers promising avenues for developing more effective treatments for trauma-related disorders.

中文翻译：

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氯胺酮通过消除 VTA 神经支配的 BLA 印迹细胞中编码的创伤记忆来改善创伤后社交回避


在记忆重新巩固过程中擦除创伤记忆是治疗创伤后应激障碍（PTSD）的一种有前景的检索-消除策略。在这里，我们开发了一种急性社交失败应激（SDS）小鼠模型，具有短期和重新暴露诱发的长期社交回避。 SDS 相关的创伤记忆被确定储存在基底外侧杏仁核 (BLA) 印迹细胞中。在重新暴露时间窗口内（但不超过重新暴露时间窗口）腹腔内单次施用亚麻醉剂量氯胺酮可显着减轻 SDS 诱导的社交回避，从而降低重新激活的 BLA 印迹细胞的活性和数量。此外，从腹侧被盖区到 BLA 的多巴胺能投射的激活或抑制有效地模拟或阻断再次暴露于氯胺酮的治疗效果，并且是多巴胺 D2 受体依赖性的。单细胞 RNA 测序表明，再次接触氯胺酮会引发 BLA 中与记忆相关的通路发生显着变化。总之，我们的研究增进了对氯胺酮如何减轻创伤后应激障碍症状的理解，并为开发更有效的创伤相关疾病治疗方法提供了有希望的途径。