提取-消退范式调节条件性恐惧记忆的神经生物学机制  

Neurobiological mechanisms in the regulation of conditioned fear memory by the retrieval-extinction paradigm

作　　者：王菡 牛家耀 唐佳豪 何雨璇 连波[3] 陈金红 孙宏伟[1] 孙琳[1] Wang Han;Niu Jiayao;Tang Jiahao;He Yuxuan;Lian Bo;Chen Jinhong;Sun Hongwei;Sun Lin(Department of Psychology,Weifang Medical University,Weifang 261053,China;Department of Clinical Medicine,Weifang Medical University,Weifang 261053,China;Department of Bioscience and Technology,Weifang Medical University,Weifang 261053,China;Department of Continuing Education,Weifang Medical University,Weifang 261053,China)

机构地区：[1]潍坊医学院心理学院,潍坊261053 [2]潍坊医学院临床医学院,潍坊261053 [3]潍坊医学院生命科学与技术学院,潍坊261053 [4]潍坊医学院继续教育学院,潍坊261053

出　　处：《中华行为医学与脑科学杂志》2022年第7期658-663,共6页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：国家自然科学基金青年项目(82101588);山东省自然科学基金(ZR2020MC218);中华医学会医学教育研究课题项(20A1209);中国科学院心理研究所结对共建开放课题(GJ202002);山东省医药卫生科技发展计划项目(2019WS594, 202002010572);潍坊医学院教育教学改革与研究项目(2019YB023);潍坊市科技发展计划项目(2021YX042);教育部心理学教指委教育教学改革项目(20221013)。

摘　　要：恐惧记忆在经过多次提取之后,会被暂时抑制,这种现象称为记忆消退。如何减少甚至消除恐惧记忆是创伤后应激障碍(post-traumatic stress disorder,PTSD)等恐惧相关疾病治疗的关键。基于巴甫洛夫恐惧调节任务的单一消退训练只能够抑制条件性恐惧记忆的表达,并不能消除已获得的条件性恐惧记忆。而基于记忆的再巩固理论所提出提取-消退范式,对恐惧记忆的擦除和改写具有更持久的效果,并且能够有效阻止恐惧记忆的返回。研究表明,提取-消退与多种神经递质受体如谷氨酸受体(glutamate receptor,GluR)、多巴胺受体(dopamine receptor,DAR)、L型电压门控钙通道(L-type voltage-gated calcium channels,LVGCCs)以及大麻素等密切相关,并且其效果也与提取-消退记忆阶段等因素有密切关联。目前对于提取的边界条件的研究大多只停留在行为学层面,分子机制等层面探究较少。文章从分子神经生物学层面出发,以记忆的不同阶段,不同类型的受体及分子机制为切入点,整理近年来与提取-消退相关的机制研究,为PTSD等恐惧相关疾病的治疗提供有价值的信号通路、分子靶点,并为更深入的研究提供科学依据。Fear memories are temporarily suppressed after repeated retrieval,a phenomenon known as memory extinction.How to reduce or even eliminate fear memory is the key to the treatment of fear related diseases such as post-traumatic stress disorder(PTSD).A single extinction training based on Pavlov's fear regulation task could only inhibit the expression of conditioned fear memory traces,but it could not eliminate the acquired conditioned fear memory.However,according to the reconsolidation theory based on memory,the retrieval-extinction paradigm has a more lasting effect on the erasure and rewriting of fear memory,and can effectively prevent the return of fear memory.Studies have shown that extraction-regression is closely related to a variety of neurotransmitter receptors such as glutamate receptor(GluR),dopamine receptor(DAR),L-type voltage-gated calcium channels(LVGCs)and cannabinoid.Moreover,its effect is closely related with factors such as retrieval-extinction memory stage.At present,most of the researches on extracted boundary conditions only stay at the level of behavior,with little understanding and exploration on the level of molecular mechanism.From the perspective of molecular neurobiology,with different stages of memory and different types of receptors and molecular mechanisms,this research reviewed the mechanisms of retrieval-extinction in recent years.It provided valuable signaling pathways,molecular targets and research directions for the treatment of fear-related diseases such as PTSD.

关 键 词：创伤后应激障碍 条件性恐惧记忆 提取-消退 谷氨酸受体 多巴胺受体 大麻素受体 

分 类 号：R338[医药卫生—人体生理学]