Fear memory attenuation: testing reconsolidation-extinction boundaries

恐惧记忆衰减：测试再巩固-消退边界

基本信息

批准号：
8389682
负责人：
Marie H. Monfils
金额：
$ 36.02万
依托单位：
UNIVERSITY OF TEXAS AT AUSTIN
依托单位国家：
美国
项目类别：
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/8389682
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 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

项目摘要

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.

描述（由申请人提供）：过度或持续的恐惧在精神疾病中很常见。尽管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病例中的创伤记忆却知之甚少，而这正是临床所关心的。我们最近设计了一种新颖的行为范式，可以减弱和防止恐惧记忆的回归。我们的结果表明，对常用的临床治疗（暴露疗法）进行细微的修改可以极大地改善结果，并减少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，我们的合作者实验室（普林斯顿大学的 Yael Niv 博士）开发了一种新的计算模型，为我们的结果提供了原则性的解释，并将有助于生成可测试的预测来完善我们的协议，并更好地理解持久性背后的机制。更新恐惧记忆。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烈、更古老和更复杂的恐惧记忆，希望它最终可以用于减轻临床人群的创伤记忆。