RATIONALE Forgetting of fear memory is a current medical therapy for posttraumatic stress disorder (PTSD), and hippocampal long-term depression (LTD) may be the underlying mechanism. Neuregulin 1 (NRG1), a trophic factor, reportedly modulates memory consolidation and synaptic plasticity. METHODS Fear memory was assessed using contextual fear conditioning. Electrophysiology was used to measure LTD and GABAergic transmission in the hippocampus. OBJECTIVES To determine the contribution of hippocampal NRG1 to fear memory forgetting and low-frequency stimulation (LFS)-induced LTD. RESULTS Administration of NRG1 in the hippocampus accelerated forgetting of contextual fear memories. Furthermore, NRG1 had no effect on low-frequency stimulation-induced LTD in young mice but significantly facilitated the induction of LTD and GABAergic transmission in adult animals. More importantly, NRG1-facilitated LTD induction in adult mice could be blocked by inhibition of GABAA receptors and NMDAR activation. CONCLUSION These findings suggest a role for NRG1 in fear memory forgetting and hippocampal LTD, providing a potential target for the development of drug-assisted PTSD therapy.

中文翻译：

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NRG1 加速恐惧记忆的遗忘并促进成年小鼠长期抑郁的诱导。

基本原理 忘记恐惧记忆是目前治疗创伤后应激障碍 (PTSD) 的一种药物疗法，海马长期抑郁症 (LTD) 可能是其潜在机制。据报道，神经调节蛋白 1 (NRG1) 是一种营养因子，可调节记忆巩固和突触可塑性。方法 使用情境恐惧条件反射评估恐惧记忆。电生理学用于测量海马中的 LTD 和 GABA 能传递。目的 确定海马 NRG1 对恐惧记忆遗忘和低频刺激 (LFS) 诱导的 LTD. 的贡献。结果 海马体中 NRG1 的给药加速了情境恐惧记忆的遗忘。此外，NRG1 对年轻小鼠低频刺激诱导的 LTD 没有影响，但显着促进了成年动物 LTD 和 GABA 能传递的诱导。更重要的是，成年小鼠中 NRG1 促进的 LTD 诱导可以通过抑制 GABAA 受体和 NMDAR 激活来阻断。结论 这些发现表明 NRG1 在恐惧记忆遗忘和海马 LTD 中的作用，为药物辅助 PTSD 治疗的发展提供了一个潜在的目标。