Mechanisms of short and long interval fear extinction

短时程和长时程恐惧消退的机制

• 批准号: 7294272
• 负责人: KARYN M MYERS
• 金额: $ 4.53万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-29 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7294272
• 关键词: Affect; Agonist; Amygdaloid structure; Animals; Anxiety Disorders; Biochemical; Clinical; Cues; Data; Dependence; Down-Regulation; Event; Exhibits; Extinction (Psychology); Fright; Interneurons; Laboratories; Learning; Localized; MAP Kinase Gene; Mediating; Memory; N-Methyl-D-Aspartate Receptors; N-Methylaspartate; NMDA receptor antagonist; NR1 NMDA receptor; NR1 gene; Neurobiology; Neurons; Organism; Prevention; Procedures; Process; Publishing; Recovery; Regulation; Resistance; Signal Transduction; System; Techniques; Therapeutic Intervention; Training; Up-Regulation; base; conditioned fear; human NR1 protein; neurobiological mechanism; novel; prevent; receptor expression; receptor function; research study; response

DESCRIPTION (provided by applicant): When a fear conditioned organism is exposed repeatedly to a fear-eliciting cue in the absence of any aversive event, the conditioned fear response declines and ultimately disappears. This process is known as fear extinction. In most cases extinction is believed to represent inhibition of fear, but extinction may involve erasure of fear if extinction training occurs very shortly after fear acquisition. Therefore, comparison of short (10 min) and long (72 hr) interval extinction may be used to elucidate the neurobiological mechanisms of fear inhibition vs. fear erasure. Preliminary data suggest differential involvement of NMDA receptors: expression of p44/42 MAPK and the NR2B (but not NR1) subunit of the NMDA receptor decreases within the amygdala following 10 min extinction, and 10 min extinction is not affected by administration of an NMDA receptor antagonist whereas 72 hr extinction is blocked. Understanding this issue will be important in terms of advancing understanding of the neurobiology of learning and memory, as well as from a clinical perspective. This proposal aims to employ a combination of biochemical and pharmacologic techniques to dissect the mechanisms of extinction as inhibition vs. erasure of fear.

描述（由申请人提供）：当条件性恐惧生物体在没有任何厌恶事件的情况下反复暴露于恐惧引发线索时，条件性恐惧反应会减弱并最终消失。这个过程被称为恐惧消退。在大多数情况下，消退被认为代表了恐惧的抑制，但如果消退训练发生在恐惧获得后不久，消退可能涉及恐惧的消除。因此，短（10 分钟）和长（72 小时）间隔消退的比较可用于阐明恐惧抑制与恐惧消除的神经生物学机制。初步数据表明 NMDA 受体的参与程度不同：10 分钟消退后，杏仁核内 p44/42 MAPK 和 NMDA 受体 NR2B（但不是 NR1）亚基的表达降低，并且 10 分钟消退不受给予 NMDA 受体的影响拮抗剂，而 72 小时消退被阻断。理解这个问题对于增进对学习和记忆的神经生物学的理解以及从临床角度来看非常重要。该提案旨在结合生化和药理学技术来剖析抑制与消除恐惧的消退机制。