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: 8777019
• 负责人: Marie H. Monfils
• 金额: $ 37.55万
• 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 2016-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8777019
• 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; Health; 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; fear memory; forgetting; improved; in vivo; learning extinction; neuromechanism; novel; prevent; 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.

描述（由申请人提供）：夸张或持续的恐惧是精神疾病中的常见。尽管通过研究帕夫洛维亚调节的研究，在发现恐惧学习的神经基础上取得了很多进展，但对于如何减少或消除病理性病例中的创伤性记忆知之甚少，这是极大的临床关注。我们最近设计了一种新颖的行为范式，可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）的细微修改可以大大改善预后，并减少患有创伤后应激障碍或特定恐惧症患者复发的潜力。同时，在我们的合作者实验室（普林斯顿大学的Yael Niv博士）中开发的一种新的计算模型为我们的结果提供了原则上的解释，并将有助于产生可测试的预测以完善我们的协议，并更好地了解持续的恐惧记忆更新的机制。在拟议的研究中，我们将首先使用计算衍生的预测来完善我们的方案。接下来，我们将测试该优化协议的限制，并检查它是否可以用来靶向更强，较旧，更复杂的恐惧记忆，并希望最终可以使用它来减轻临床人群中的创伤性记忆。

项目成果

Assessing Fear Following Retrieval + Extinction Through Suppression of Baseline Reward Seeking vs. Freezing.

• DOI: 10.3389/fnbeh.2015.00355
• 发表时间: 2015
• 期刊: Frontiers in behavioral neuroscience
• 影响因子: 3
• 作者: Shumake J;Monfils MH
• 通讯作者: Monfils MH

The roots of empathy: Through the lens of rodent models.

• DOI: 10.1016/j.neubiorev.2016.10.028
• 发表时间: 2017-05
• 期刊: Neuroscience and biobehavioral reviews
• 影响因子: 8.2
• 作者: Meyza KZ;Bartal IB;Monfils MH;Panksepp JB;Knapska E
• 通讯作者: Knapska E

Dominance status predicts social fear transmission in laboratory rats.

• DOI: 10.1007/s10071-016-1013-2
• 发表时间: 2016-11
• 期刊: ANIMAL COGNITION
• 影响因子: 2.7
• 作者: Jones, Carolyn E.;Monfils, Marie-H.
• 通讯作者: Monfils, Marie-H.

Post-retrieval extinction in adolescence prevents return of juvenile fear.

• DOI: 10.1101/lm.043281.116
• 发表时间: 2016-10
• 期刊: Learning & memory (Cold Spring Harbor, N.Y.)
• 作者: Jones CE;Monfils MH
• 通讯作者: Monfils MH