Neural Mechanisms of Escape From Fear Learning

描述（申请人提供）：巴甫洛夫条件恐惧被广泛用于研究联想学习和焦虑的神经机制。条件性恐惧通常是由中性条件刺激（CS）与厌恶的非条件刺激配对引起的。随后的CS演示引起了恐惧反应。虽然这项研究很重要，但它忽略了一类与人类恐惧病理和应对直接相关的学习：恐惧驱动的工具学习。从恐惧中逃脱（EFF）任务是将这种学习与恐惧习得分开来研究的。在EFF中，动物被呈现出引发恐惧的CSs，当它们做出特定反应时，这些CSs就会终止。因此，cs终止取决于主动反应，或者更正式地说，条件负强化支持反应学习。本提案概述了使用优化的EFF程序、病变、失活和单单元记录对负责EFF学习的神经回路的调查。最初的重点将是杏仁核（对恐惧调节至关重要的核）和纹状体（与工具学习相关的区域）之间的相互作用。研究结果将进一步加深我们对恐惧学习的理解，对人类治疗具有潜在的重要意义。

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.