情感和记忆环路的失调会引发一系列病理性记忆相关疾病，如创伤后应激障碍综合征（PTSD）等。目前在临床中，基于记忆消退理论的暴露疗法常用来治疗PTSD等精神疾病，但疗效有限，随着时间的推移病理性记忆会重现。其关键原因在于该疗法只是抑制了原有的记忆，并没有彻底消除病理性记忆。因此探索调控恐惧记忆消退的神经环路，发展新的可消除记忆的心理学范式是亟待解决的重大科学问题。我们前期研究发现非条件性线索唤起-消退心理学范式可以消除恐惧记忆，同时我们还发现在睡眠中可发生记忆的消退，但是其神经机制尚不清楚。因此，我们拟通过在体多通道记录、可视化记忆标记及微环路示踪等技术探索唤起-消退模式消除恐惧记忆的神经编码机制；同时应用睡眠脑电，光遗传和神经影像学等技术，结合动物和人体研究，探索睡眠与清醒状态下恐惧记忆消退神经微环路机制的异同，进而综合记忆唤起-消退和睡眠记忆消退范式的优势，发展有效的无创记忆消除范式。

Dysfunction of emotional and memory circuits leads to a serial pathological memory-related disease, such as posttraumatic stress disorder (PTSD). In clinic, the exposure therapy, which is based on the theory of memory formation and extinction, has been used for the treatment of PTSD and phobia disorder. However, the effectiveness of the therapy is limited, and the pathological memory and the PTSD syndromes often spontaneously re-emerge after some passages of time. The key reason is that exposure-therapy inhibits the expression of original fear but does not erase the fear memory trace. Thus, it has been crucial scientific question that what is the key circuits of memory extinction, and how to enhance the process of memory extinction to erase fear memory with a non-pharmacological manner. Our previous studies have showed that unconditioned stimulus-induced memory retrieval-extinction procedure erases original fear memory, and prevents the return of fear response; additionally, we also found repeated exposure of conditioned stimulus during sleep leads to memory extinction. However, the neurobiological mechanisms underlying these findings remain unknown. In the present project, we will use multiple tools, including in vivo spike recording, visualized mapping of memory trace and tracing of memory circuits, to investigate neuronal encoding mechanisms of retrieval-extinction procedure; we will also combine the electroencephalogram, optogenetics and functional magnetic resonance imaging in rodent and/or human studies, to elucidate the distinct brain circuits of fear extinction during wakefulness and sleep status. Our aim is to integrate the procedures of memory retrieval-extinction and memory extinction in sleep to develop a new noninvasive and effective paradigm for the treatment of pathological memory-related disease.