Neural Mechanisms of Escape From Fear Learning

描述(申请人提供)：巴甫洛夫条件性恐惧被广泛用于研究联想学习和焦虑的神经机制。条件性恐惧通常是通过将中性条件刺激(CS)与厌恶的无条件刺激配对而产生的。随后对CS的陈述引发了恐惧反应。虽然这项研究很重要，但它忽略了与人类恐惧病理和应对直接相关的一类学习：恐惧动机的工具性学习。从恐惧中逃离(Eff)任务是为了研究这种学习与恐惧习得分开进行的。在EFF中，动物被呈现在引发恐惧的CS中，当它们做出特定的反应时，这些CS就会终止。因此，CS终止取决于积极反应，或者更正式地说，条件性否定强化支持反应学习。该提案概述了使用优化的EFF程序、损伤、灭活和单单位记录对负责EFF学习的神经回路进行的研究。最初的焦点将是杏仁核和纹状体之间的相互作用，杏仁核是恐惧条件反射的关键核，纹状体是与工具性学习有关的区域。这一结果应该会加深我们对恐惧学习的理解，这可能会对人类的治疗产生重要影响。

DESCRIPTION (provided by applicant): Pavlovian conditioned fear is widely used to study the neural mechanisms of associative learning and anxiety. Conditioned fear is typically induced by pairing a neutral conditioned stimulus (CS) with an aversive unconditioned stimulus. Subsequent presentations of the CS elicit fear reactions. While this research is important, it neglects a class of learning with direct relevance to fear pathology and coping in humans: fear-motivated instrumental learning. The Escape From Fear (EFF) task was developed to study this learning separately from fear acquisition. In EFF, animals are presented with fear-eliciting CSs that terminate when they make a specific response. Thus, CS-termination is contingent upon active responding, or more formally, conditioned negative reinforcement supports response learning. This proposal outlines an investigation of the neural circuits responsible for EFF learning using an optimized EFF procedure, lesions, inactivations and single-unit recordings. The initial focus will be interactions between the amygdala, a nucleus critical for fear conditioning, and striatum, a region linked to instrumental learning. The results should further our understanding of fear learning with potentially important implications for human treatment.