Cortical circuitry and mechanisms underlying remote cue-specific fear memory and extinction

远程线索特异性恐惧记忆和消退背后的皮层电路和机制

• 批准号: 9815038
• 负责人: Allan T Gulledge
• 金额: $ 49.65万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9815038
• 关键词: Address; Anatomy; Auditory; Auditory area; Brain; Brain region; Communication; Cues; Data; Dependence; Development; Disease; Distal; Emotional; Event; Exposure to; Extinction (Psychology); Fright; Human; Individual; Laboratories; Lateral; Lead; Life; Light; Mediating; Memory; Methods; Modeling; Neurons; Opsin; Outcome; Persons; Plague; Post-Traumatic Stress Disorders; Rattus; Research; Retrieval; Sensory; Shock; Stimulus; Support System; System; Testing; Theoretical model; Time; Trauma; Visual; Visual Cortex; Work; auditory stimulus; base; combat; conditioned fear; effective therapy; experience; experimental study; fear memory; immunocytochemistry; innovation; neural circuit; neural model; neuromechanism; novel; optogenetics; relating to nervous system; response; sensory cortex; sensory input; sensory stimulus; sexual assault; sound; traumatic event; visual stimulus

Project Summary Individuals with fear disorders such as post-traumatic stress disorder (PTSD) experience excessively strong and intrusive fear memories about stimuli that were encountered during a prior trauma, including individual sounds or visual stimuli (“cue-specific” fear memory) or the combination of stimuli that together define the place in which the event occurred (“contextual” fear memory). The memories may have been formed recently or long ago (“remote” memories), in which case they may plague a person for a substantial portion of his/her life. The development of effective therapies depends on a thorough understanding the neural mechanisms that underlie these different types of fear memories, as well as fear extinction, which is the basis for exposure- based therapy commonly used to reduce fear in humans. To date, a substantial body of research has identified discrete neural systems that support recent versus remote contextual memory, and other studies have identified the substrates of recently-acquired cue-specific memory and extinction, but very little work has focused on the brain mechanisms involved in remote cue- specific memory and extinction. This is important to resolve particularly with respect to PTSD since individuals often do not seek therapy until long after the traumatic event, especially in cases of combat trauma or sexual assault. To address this, the proposed research advances a new theoretical model of the neural circuits that underlie remote cue-specific fear memory and extinction. This model is based on new data from our laboratory and combines state-of-the art chemogenetic and optogentic-anatomical approaches to test the hypotheses that a) communication between the retrosplenial cortex and secondary sensory cortices is necessary for remote cue-specific fear memory, and b) the postrhinal cortex mediates the context-dependency of extinction of remote cue-specific fear.

项目概要 患有恐惧症（例如创伤后应激障碍（PTSD））的人 对之前遇到的刺激有过分强烈和侵入性的恐惧记忆 创伤，包括个人声音或视觉刺激（“特定线索”恐惧记忆）或 共同定义事件发生地点的刺激组合（“情境恐惧”） 记忆）可能是最近或很久以前形成的（“远程”记忆）。 在这种情况下，它们可能会困扰一个人一生的大部分时间。 有效的治疗取决于对潜在神经机制的透彻理解 这些不同类型的恐惧记忆，以及恐惧消退，这是暴露的基础—— 迄今为止，已有大量研究表明，这种疗法通常用于减少人类的恐惧。 已经确定了支持最近与远程上下文记忆的离散神经系统，并且 其他研究已经确定了最近获得的线索特异性记忆的基础 灭绝，但很少有研究关注涉及远程提示的大脑机制 解决特定记忆和消退问题尤其重要。 因为人们通常要等到创伤事件发生很久之后才寻求治疗，尤其是在某些情况下 为了解决这个问题，拟议的研究提出了一项新的研究。 远程提示特定恐惧记忆背后的神经回路的理论模型 该模型基于我们实验室的新数据，并结合了最先进的技术。 化学遗传学和光遗传学解剖方法来检验以下假设： 压后皮层和次级感觉皮层之间的交流对于 远程提示特定的恐惧记忆，b）鼻后皮层介导情境依赖性 远程提示特定恐惧的消失。