Induction of Conditional Fear Extinction

描述(申请人提供)：自从巴甫洛夫以来，哺乳动物中的条件性恐惧 一直是联想学习和人类焦虑的重要模型。 简而言之，动物迅速学会害怕中性条件刺激(CS)， 例如语气，当它在时间上与厌恶的无条件的 刺激(美国)，通常是轻微的脚部电击。随后暴露于 CS-单独在啮齿动物中引起强烈的条件性恐惧反应(CR)，包括 冻结行为。反复接触CS可使CR增强 (孵化)或减弱(灭绝)取决于时间模式 曝光。消除恐惧是一个积极的学习过程，导致 形成一种抑制记忆，阻止恐惧的表达。这项建议 将集中在导致物种灭绝的细胞机制上 回忆。目标1将尝试定义CS暴露的最小量 有必要通过一系列简单的行为来诱导消亡记忆 实验。目标2将研究杏仁核的潜在作用 消失中的突触后L型电压门控钙通道(L-VGCC) 记忆诱导，采用全身和局部输注L-VGCC拮抗剂。 既然消退是焦虑行为治疗的显性模式 这一发现可能会为改进心理疗法提供基础 和辅助治疗。

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.