Induction of Conditional Fear Extinction

描述（由申请人提供）：自巴甫洛夫以来，哺乳动物的条件性恐惧 一直是联想学习和人类焦虑的重要模型。 简单地说，动物很快学会害怕中性条件刺激（CS）， 例如一个音调，当它在时间上与一个厌恶的无条件音配对时 刺激（US），通常为轻度电击脚。随后暴露于 CS单独在啮齿类动物中激发了强烈的条件性恐惧反应（CR），包括 冻结行为随着CS的反复暴露，CR可以增强 （孵化）或减弱（灭绝）取决于时间模式， 暴露。消除恐惧是一个积极的学习过程， 形成抑制性记忆，阻止恐惧表达。这项建议 将集中在细胞机制的诱导灭绝 回忆目标1将尝试定义CS暴露的最小量 通过一系列简单的行为刺激来诱发记忆消失 实验目的2：探讨杏仁核的潜在作用 突触后L型电压门控钙通道（L-VGCC）在消退中的作用 记忆诱导，使用L-VGCC拮抗剂的全身和局部输注。 由于消退是焦虑行为治疗的外显模型， 这些发现可能为改善心理疗法提供基础 和预防性治疗。

DESCRIPTION (provided by applicant): Since Pavlov, conditional fear in mammals has been an important model of both associative learning and human anxiety. Briefly, animals rapidly learn to fear a neutral conditional stimulus (CS), such as a tone, when it is temporally paired with an aversive unconditional stimulus (US), typically a mild footshock. A subsequent exposure to the CS-alone elicits a robust conditional fear response (CR) in rodents, including freezing behavior. With repeated CS exposures the CR can strengthen (incubation) or weaken (extinction) depending on the temporal pattern of exposures. Extinction of fear is an active learning process resulting in the formation of an inhibitory memory that blocks fear expression. This proposal will focus on the cellular mechanisms underlying the induction of extinction memories. Aim 1 will attempt to define the minimum amount of CS exposure necessary to induce an extinction memory through a series of simple behavioral experiments. Aim 2 will investigate the potential role of amygdalar post-synaptic L-type voltage gated calcium channels (L-VGCC) in extinction memory induction, using systemic and local infusion of L-VGCC antagonists. Since extinction serves as the explicit model for behavior therapy of anxiety disorders, the findings may provide a foundation for improved psyhotherapies and adjunctive treatments.