Mechanisms of short and long interval fear extinction

描述（由申请人提供）：当恐惧条件生物体在没有任何厌恶事件的情况下反复暴露于引发恐惧的线索时，条件恐惧反应下降并最终消失。这个过程被称为恐惧消退。在大多数情况下，灭绝被认为是对恐惧的抑制，但如果灭绝训练在获得恐惧后不久发生，灭绝可能涉及恐惧的消除。因此，短（10分钟）和长（72小时）的间隔灭绝的比较可以用来阐明恐惧抑制与恐惧擦除的神经生物学机制。初步数据表明，NMDA受体的差异参与：表达的p44/42 MAPK和NR 2B（但不NR 1）的NMDA受体亚基减少杏仁核内10分钟灭绝后，和10分钟灭绝不受影响的NMDA受体拮抗剂的管理，而72小时灭绝被封锁。理解这个问题对于促进学习和记忆的神经生物学的理解以及从临床角度来看都很重要。这项建议旨在采用生物化学和药理学技术相结合的方式来剖析灭绝的机制，即抑制与消除恐惧。

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.