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: 10401949
• 负责人: Allan T Gulledge
• 金额: $ 50.41万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC 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/10401949
• 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 trauma; 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.

项目总结