PTSD样记忆损害形成的新机制：海马-杏仁体回路NE-GCs信号系统的调控作用

Post-traumatic stress disorder (PTSD) is one of the serious mental disorders with disability, and often need to be evaluated as mental injury case for the compensation. Traumatic hypermnesia for the events, peritraumatic amnesia (PTA) and subsequent increased fear memory generalization are often observed in PTSD patients. There are rich dual nerve fiber projections in hippocampus-amygdala circuit, involving encoding, consolidation and retrieval of emotional episodic memory. Basolateral amygdala (BLA) is activated by both ascending locus coeruleus (LC)-noradrenergic (NE) signaling and circulating glucocorticoids (GCs). We'll focus on the key role of GCs in PTSD-like memory impairments, propose a new hypothesis about balance of NE-GCs signaling in amygdala-hippocampal circuit for further understanding of hippocampal prioritized processing selectivity of emotional episodic memories. This project will adopt PTSD-like memory animal model, hope to get solid evidence of GCs key role, explore transform of nerve activity from hippocampus to BLA, and then clarify cellular and molecular mechanisms of emotional information processing of hippocampus and NE-GCs regulatory mechanisms.

创伤后应激障碍（PTSD）是严重损害劳动能力的精神损伤疾病。PTSD患者可表现为创伤性记忆增强和环创伤性遗忘，并继发恐惧记忆的泛化。海马-杏仁体回路涉及情绪性记忆编码、巩固及提取，两者之间存在丰富的双向神经联系。来自脑干蓝斑的去甲肾上腺素（NE）能神经释放NE，与糖皮质激素（GCs）共享cAMP/PKA-CREB细胞信号通路，共同作用于杏仁体。我们紧紧围绕"PTSD样记忆损害"这一核心症状，从背侧海马GCs的关键启动作用入手，提出了"海马-杏仁体回路NE-GCs信号系统的平衡机制"假设，解释海马对情绪性事件信息优先处理的选择性。希望通过本项目获得海马高GCs发挥关键作用的明确证据和海马-杏仁体回路神经活动转移的生物学意义，阐明NE-GCs信号系统在海马分析加工情绪性记忆的调控机制，阐明情绪性记忆的细胞分子机制，为精神损伤的伤病关系与伤残客观评定提供科学依据。

创伤后应激障碍（PTSD）是严重损害劳动能力的精神损伤疾病。PTSD患者可表现为创伤性记忆增强和环创伤性遗忘，并继发恐惧记忆的泛化。海马-杏仁体回路涉及情绪性记忆编码、巩固及提取，两者之间存在丰富的双向神经联系。来自脑干蓝斑的去甲肾上腺素（NE）能神经释放NE，与糖皮质激素（GCs）共享cAMP/PKA-CREB 细胞信号通路，共同作用于杏仁体。本项目紧紧围绕“PTSD 样记忆损害”这一核心症状，采用行为药理神学、分子生物学等技术，首先确定参与PTSD样记忆损害形成的关键脑区包括：海马CA1区、杏仁体BLA区及前额叶IL区。进一步明确高水平的GCs可能通过 GR信号转导通路调控PTSD样记忆损害的形成。在PTSD样记忆损害形成巩固阶段，海马去甲肾上腺素能β受体并不参与GCs诱导PTSD样记忆损害形成。单独适度拮抗海马NE系统即可启动PTSD 样记忆损害形成，并伴随前额叶-海马-杏仁体环路的神经活动方式的改变。而在BLA区直接给予中等剂量的NE即可诱导PTSD样记忆损害的形成，并可能是通过调节cAMP-PKA和CaMK II-PKC信号通路实现的。综上，通过本项目，我们获得了海马高GCs 发挥关键作用的明确证据，初步阐明了GCs系统和NE信号系统在海马分析加工情绪性记忆的调控机制，加深了对情绪性记忆的细胞分子机制的认识，为PTSD的治疗和预防提供了新的药物靶点，为精神损伤的伤病关系与伤残客观评定提供科学依据。