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Abstract：
Posttraumatic stress disorder (PTSD) is a debilitating psychosomatic condition characterized by impairment of brain fear circuits and persistence of exceptionally strong associative memories resistant to extinction. In this study, we investigated the neural and behavioral consequences of inhibiting protein synthesis, a process known to suppress the formation of conventional aversive memories, in an established PTSD animal model based on contextual fear conditioning in mice. Control animals were subjected to the conventional fear conditioning task. Utilizing c-Fos neural activity mapping, we found that the retrieval of PTSD and normal aversive memories produced activation of an overlapping set of brain structures. However, several specific areas, such as the infralimbic cortex and the paraventricular thalamic nucleus, showed an increase in the PTSD group compared to the normal aversive memory group. Administration of protein synthesis inhibitor before PTSD induction disrupted the formation of traumatic memories, resulting in behavior that matched the behavior of mice with usual aversive memory. Concomitant with this behavioral shift was a normalization of brain c-Fos activation pattern matching the one observed in usual fear memory. Our findings demonstrate that inhibiting protein synthesis during traumatic experiences significantly impairs the development of PTSD in a mouse model. These data provide insights into the neural underpinnings of protein synthesis-dependent traumatic memory formation and open prospects for the development of new therapeutic strategies for PTSD prevention.
摘要：
创伤后应激障碍（PTSD）是一种使人衰弱的心身疾病，其特征是大脑恐惧回路受损，并且持续存在抵抗灭绝的异常强烈的联想记忆。在这项研究中,我们研究了抑制蛋白质合成的神经和行为后果，一种已知的抑制传统厌恶记忆形成的过程，在基于上下文恐惧条件的小鼠建立的PTSD动物模型中。对对照动物进行常规的恐惧调节任务。利用c-Fos神经活动映射，我们发现,创伤后应激障碍和正常厌恶记忆的恢复会激活一组重叠的大脑结构.然而,几个具体领域，如脑下皮质和脑室旁丘脑核，与正常厌恶记忆组相比，PTSD组增加。在PTSD诱导前施用蛋白质合成抑制剂破坏了创伤记忆的形成，导致小鼠的行为与通常的厌恶记忆相匹配。伴随这种行为转变的是大脑c-Fos激活模式的正常化，与通常的恐惧记忆中观察到的模式相匹配。我们的发现表明，在创伤经历期间抑制蛋白质合成会显着损害小鼠模型中PTSD的发展。这些数据提供了对蛋白质合成依赖性创伤性记忆形成的神经基础的见解，并为开发PTSD预防的新治疗策略开辟了前景。
