Fear memory attenuation: testing reconsolidation-extinction boundaries

恐惧记忆衰减：测试再巩固-消退边界

• 批准号: 8204555
• 负责人: Marie H. Monfils
• 金额: $ 38.01万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-12-06 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8204555
• 关键词: Amygdaloid structure; Animals; Attenuated; Behavior; Behavioral; Behavioral Paradigm; Biological Neural Networks; Clinical; Clinical Treatment; Complex; Computer Simulation; Conditioned Stimulus; Effectiveness; Emotional; Extinction (Psychology); Fluorescent in Situ Hybridization; Freezing; Fright; Future; Hippocampus (Brain); Homer 1a; Hour; Immediate-Early Genes; Individual; Knowledge; Laboratories; Lateral; Learning; Maps; Medial; Memory; Mental disorders; Messenger RNA; Modification; Outcome; Pharmaceutical Preparations; Population; Post-Traumatic Stress Disorders; Prefrontal Cortex; Process; Protocols documentation; Public Health; Relapse; Research; Retrieval; Sensory; Series; Shock; Specific Phobia; Stimulus; Structure; Techniques; Testing; Time; Training; Universities; Update; Work; Writing; attenuation; base; classical conditioning; clinical efficacy; coping mechanism; forgetting; improved; in vivo; learning extinction; neuromechanism; novel; prevent; public health relevance; relating to nervous system; research study; response

DESCRIPTION (provided by applicant): Exaggerated or persistent fear is a common occurrence in psychiatric disorders. Although much progress has been made in uncovering the neural basis of fear learning through studies of Pavlovian conditioning, little is known about how to reduce or eliminate traumatic memories in pathological cases, which is of great clinical concern. We have recently devised a novel behavioral paradigm that attenuates and prevents the return of fear memories. Our results indicate that subtle modifications to a commonly employed clinical treatment (exposure therapy) could greatly improve outcome, and reduce the potential for relapse in individuals suffering from post-traumatic stress disorder or specific phobias. In parallel, a new computational model developed in our collaborator's lab (Dr. Yael Niv, at Princeton University) provides a principled explanation for our results, and will help generate testable predictions to refine our protocol, and better understand the mechanisms that underlie the persistent updating of fear memories. In the proposed studies, we will first refine our protocol using computationally-derived predictions. Next, we will test the limits of this optimized protocol, and examine whether it may be used to target stronger, older, and more complex fear memories, with the hopes that it may eventually be employed to attenuate traumatic memories in clinical populations. PUBLIC HEALTH RELEVANCE: Exaggerated or persistent fear is a common occurrence in psychiatric disorders. Two paradigms (blockade of reconsolidation and extinction) have been used in the laboratory setting to reduce acquired fear; however, the clinical efficacy of these techniques has been limited. We have recently presented a novel behavioral paradigm that attenuates and prevents the return of fear memories by combining reconsolidation and extinction principles (Ret+Ext). Our findings suggest that subtle modifications to a commonly employed clinical treatment (exposure therapy) could greatly improve outcome, and reduce the potential for relapse in individuals suffering from post-traumatic stress disorder or specific phobias. Here, we propose to extend these findings to isolate the neural mechanisms that underlie our fear-reducing treatment, and to closely examine the strengths, weaknesses, and possible consequences of using this Ret+Ext paradigm.

描述（由申请人提供）：夸大或持续的恐惧是精神疾病中常见的现象。虽然通过巴甫洛夫条件反射的研究在揭示恐惧学习的神经基础方面取得了很大进展，但对于如何减少或消除病理情况下的创伤记忆知之甚少，这是一个非常重要的临床问题。我们最近设计了一种新的行为模式，可以减弱和防止恐惧记忆的回归。我们的研究结果表明，对常用的临床治疗（暴露疗法）进行细微的修改可以大大改善结果，并降低患有创伤后应激障碍或特定恐惧症的个体复发的可能性。与此同时，在我们的合作者实验室（普林斯顿大学的Yael Niv博士）开发的一种新的计算模型为我们的结果提供了一个原则性的解释，并将有助于生成可测试的预测来完善我们的协议，并更好地理解恐惧记忆持续更新的机制。在拟议的研究中，我们将首先使用计算得出的预测来完善我们的协议。接下来，我们将测试这种优化方案的局限性，并检查它是否可以用于针对更强，更老，更复杂的恐惧记忆，希望它最终可以用于减轻临床人群的创伤记忆。 公共卫生相关性：夸大或持续的恐惧在精神疾病中很常见。两种范例（阻断再巩固和消退）已被用于在实验室设置，以减少获得性恐惧，然而，这些技术的临床疗效有限。我们最近提出了一种新的行为范式，通过结合再巩固和灭绝原则（Ret+Ext）来衰减和防止恐惧记忆的回归。我们的研究结果表明，对常用的临床治疗（暴露疗法）进行细微的修改可以大大改善结果，并降低患有创伤后应激障碍或特定恐惧症的个体复发的可能性。在这里，我们建议扩展这些发现，以隔离我们减少恐惧治疗的神经机制，并仔细检查使用这种Ret+Ext范式的优点，缺点和可能的后果。