Chang Shao-Han, Chen Huan-Yuan, Shaw Fu-Zen, Shyu Bai-Chuang
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Department of Psychology, National Cheng Kung University, Tainan, Taiwan.
Neurobiol Stress. 2023 Jul 22;26:100554. doi: 10.1016/j.ynstr.2023.100554. eCollection 2023 Sep.
Posttraumatic stress disorder (PTSD) is a complex syndrome that may occur after life-threatening events. Fear memory abnormalities may play vital roles in the pathogenesis of PTSD. Previous work has found that fear memories are not rigid; the retrieval of fear memories may change over time. Furthermore, prior studies suggest that theta wave (4 Hz) activity is highly correlated with fear expression in an animal model. However, the relationship between pathological fear memory and potential brain wave features in PTSD remains largely uncharacterized. Here, we hypothesized that after traumatic stress exposure, the longitudinal dynamics of abnormal fears in PTSD animal models could be reflected by the measurement of local field potentials (LFPs). Using a well-established modified single-prolonged stress and footshock (SPS & FS) PTSD rat model, animals were restrained for 2 h and subsequently subjected to 20 min of forced swimming, then exposed to diethyl ether until they lost consciousness and placed in a conditioning chamber for fear conditioning. To characterize the temporal changes, we characterized freezing behavior brain wave features during the conditioning chamber re-exposure in the early (10 and 30 min; 2, 4, and 6 h) and late (day 1, 3, 7, and 14) phases after traumatic stress exposure. Our results indicate that SPS & FS rats showed co-morbid PTSD phenotypes including significantly higher levels of anxiety-, depression-, and anhedonia-like behaviors, and impaired fear extinction. Delta wave (0.5-4 Hz) suppression in the medial prefrontal cortex, amygdala, and ventral hippocampus occurred 10 and 30 min after traumatic stress, followed by continuous delta wave activity from 2 h to day 14, correlating with fear levels. tDCS reduced delta activity and alleviated PTSD-like phenotypes in the SPS & FS group. In this study, profiling abnormal fears with brain wave correlates may improve our understanding of time-dependent pathological fear memory retrieval in PTSD and facilitate the development of effective intervention strategies.
创伤后应激障碍（PTSD）是一种可能在危及生命的事件后发生的复杂综合征。恐惧记忆异常可能在PTSD的发病机制中起重要作用。先前的研究发现，恐惧记忆并非一成不变；恐惧记忆的提取可能随时间而变化。此外，先前的研究表明，在动物模型中，θ波（4Hz）活动与恐惧表达高度相关。然而，PTSD中病理性恐惧记忆与潜在脑电波特征之间的关系在很大程度上仍未得到充分描述。在此，我们假设在创伤性应激暴露后，通过测量局部场电位（LFP）可以反映PTSD动物模型中异常恐惧的纵向动态变化。使用一种成熟的改良单次长时间应激和足部电击（SPS & FS）PTSD大鼠模型，将动物束缚2小时，随后进行20分钟的强迫游泳，然后暴露于乙醚中直至失去意识，并放置在条件反射箱中进行恐惧条件反射。为了表征时间变化，我们在创伤性应激暴露后的早期（10和30分钟；2、4和6小时）和晚期（第1、3、7和14天）阶段，对条件反射箱重新暴露期间的僵住行为脑电波特征进行了表征。我们的结果表明，SPS & FS大鼠表现出共病的PTSD表型，包括焦虑、抑郁和快感缺失样行为水平显著更高，以及恐惧消退受损。创伤性应激后10和30分钟，内侧前额叶皮质、杏仁核和腹侧海马体中的δ波（0.5 - 4Hz）受到抑制，随后从2小时到第14天持续出现δ波活动，这与恐惧水平相关。经颅直流电刺激（tDCS）降低了δ波活动，并减轻了SPS & FS组的PTSD样表型。在本研究中，通过脑电波相关性分析异常恐惧可能会增进我们对PTSD中时间依赖性病理性恐惧记忆提取的理解，并促进有效干预策略的开发。
