Prediction error in contextual fear memory reconsolidation

情境恐惧记忆再巩固的预测错误

• 批准号: 8497120
• 负责人: Jennifer J Quinn
• 金额: $ 40.11万
• 依托单位: MIAMI UNIVERSITY OXFORD
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-15 至 2017-06-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8497120
• 关键词: Address; Afghanistan; Amygdaloid structure; Aversive Stimulus; Basic Science; Behavioral; Behavioral Mechanisms; Brain; Cognitive Therapy; Development; Discrimination; Expectancy; Extinction (Psychology); Fright; Future; General Population; Genetic Research; Gulf War; Investigation; Iraq; Learning; Memory; Natural Disasters; Opioid Receptor; Outcome; Patients; Play; Post-Traumatic Stress Disorders; Prevalence; Procedures; Process; Psychological reinforcement; Research; Research Personnel; Retrieval; Role; Services; Sexual abuse; Shock; Signal Transduction; System; Therapeutic Intervention; Time; Training; Trauma; Update; Veterans; Vietnam; base; combat; effective therapy; expectation; experience; innovation; interest; long term memory; member; memory process; memory retrieval; midbrain central gray substance; neural circuit; neurobiological mechanism; novel; physical abuse; public health relevance; receptor; research study; surgical research

DESCRIPTION (provided by applicant): In the past 15 years, neurobiologists have challenged the view that memories stabilize over time through a process of consolidation; recent research indicates that memories undergo a period of restabilization following reactivation/retrieval that i distinct from initial consolidation. Termed "reconsolidation," this process appears to be evolutionarily conserved and dynamic - maintaining, strengthening, and/or updating existing memories in order to preserve their predictive relevance. Reconsolidation is of interest to researchers and clinicians, in part because it holds tremendous promise for those who suffer from intrusive and often debilitating memories, such as patients with post-traumatic stress disorder (PTSD). Reconsolidation research has the potential to inform and facilitate cognitive-behavioral therapy, resulting in better outcomes for PTSD sufferers. Unfortunately, the basic behavioral and neurobiological mechanisms of reconsolidation are poorly understood. However, preliminary investigations by our lab and others suggest an important role for prediction error (i.e., surprise, or the violation of expectation), in the initiation of memory reconsolidation processes. If reconsolidation provides a mechanism for the updating of existing memories, then new (i.e., not already predicted) information must be present in order for reconsolidation processes to be initiated. Using a combination of behavioral, anatomical and pharmacological approaches, we propose a systematic analysis of the neural circuits responsible for the prediction error signal that triggers reconsolidation of contextual fear memories. In Aim 1, we wil examine contextual fear memory reconsolidation following an unexpected retrieval. We hypothesize that reactivation of a contextual fear memory in an unexpected manner will initiate fear memory reconsolidation processes in the basolateral amygdala (BLA). Either the omission of an expected outcome or the substitution of an expected outcome with a different aversive stimulus will initiate reconsolidation. Further, we hypothesize that BLA expression of both zif268 and Arc/Arg3.1 will be elevated following an unexpected reactivation session. In Aim 2, we will define the role of ventrolateral periaqueductal gray (vlPAG) opioid receptors in triggering contextual fear memory reconsolidation following an unexpected retrieval. We hypothesize that vlPAG opioid receptors trigger amygdalar reconsolidation of fear memories during memory reactivation that violates an expectation. In Aim 3, we will define the role of the orbitofrontal cortex (OFC) in triggering contextual fear memory reconsolidation following an unexpected retrieval. We hypothesize that the OFC will play a critical role in signaling outcome expectancy and thereby triggering BLA reconsolidation processes when the reactivation session violates an expected outcome. Our application represents a major conceptual innovation, as it is the first to look at reconsolidation as the product of interacting components of an integrated error-correction circuit.

描述（由申请人提供）：在过去 15 年中，神经生物学家对记忆通过巩固过程随着时间的推移而稳定的观点提出了挑战。最近的研究表明，记忆在重新激活/检索后会经历一段重新稳定的时期，这与最初的巩固不同。这个过程被称为“重新巩固”，似乎在进化上是保守的和动态的——维持、加强和/或更新现有的记忆，以保持它们的预测相关性。研究人员和临床医生对重新巩固很感兴趣，部分原因是它为那些遭受侵入性记忆和经常使人衰弱的记忆的人带来了巨大的希望，例如患有创伤后应激障碍（PTSD）的患者。再巩固研究有可能为认知行为治疗提供信息和促进，从而为创伤后应激障碍患者带来更好的结果。不幸的是，人们对再巩固的基本行为和神经生物学机制知之甚少。然而，我们实验室和其他人的初步调查表明，预测错误（即意外或违反预期）在记忆重新巩固过程的启动中发挥着重要作用。如果重新巩固提供了更新现有记忆的机制，那么必须存在新的（即尚未预测的）信息才能启动重新巩固过程。结合行为、解剖和药理学方法，我们提出对负责预测错误信号的神经回路进行系统分析，该信号触发情境恐惧记忆的重新巩固。在目标 1 中，我们将检查意外检索后情境恐惧记忆的重新巩固。我们假设以意想不到的方式重新激活情境恐惧记忆将启动基底外侧杏仁核（BLA）的恐惧记忆重新巩固过程。遗漏预期结果或用不同的厌恶刺激替代预期结果都会引发重新巩固。此外，我们假设 zif268 和 Arc/Arg3.1 的 BLA 表达在意外的重新激活过程后都会升高。在目标 2 中，我们将定义腹外侧导水管周围灰质 (vlPAG) 阿片受体在意外检索后触发情景恐惧记忆重新巩固中的作用。我们假设 vlPAG 阿片受体在违反预期的记忆重新激活过程中触发杏仁核恐惧记忆的重新巩固。在目标 3 中，我们将定义眶额皮层 (OFC) 在意外检索后触发情景恐惧记忆重新巩固中的作用。我们假设 OFC 将在发出结果预期信号方面发挥关键作用，从而在重新激活会话违反预期结果时触发 BLA 重新巩固过程。我们的应用代表了一项重大的概念创新，因为它是第一个将重新整合视为集成纠错电路的交互组件的产物。

项目成果

Differential Effects of Lateral and Medial Entorhinal Cortex Lesions on Trace, Delay and Contextual Fear Memories.

外侧和内侧内嗅皮层损伤对痕迹、延迟和情境恐惧记忆的不同影响。

• 发表时间: 2021-12-28
• 影响因子: 3.3
• 作者: East Jr, Brett S;Brady, Lauren R;Quinn, Jennifer J
• 通讯作者: Quinn, Jennifer J

The amygdala is critical for trace, delay, and contextual fear conditioning.

杏仁核对于追踪、延迟和情境恐惧调节至关重要。

• 发表时间: 2015-02
• 作者: Kochli, Daniel E;Thompson, Elaine C;Fricke, Elizabeth A;Postle, Abagail F;Quinn, Jennifer J
• 通讯作者: Quinn, Jennifer J

Combined administration of MK-801 and cycloheximide produces a delayed potentiation of fear discrimination memory extinction.

MK-801 和放线菌酮联合给药可延迟增强恐惧辨别记忆消退。

• 发表时间: 2018-04
• 影响因子: 1.9
• 作者: Kochli, Daniel E;Campbell, Tiffany L;Hollingsworth, Ethan W;Lab, Rain S;Postle, Abagail F;Perry, Megan M;Mordzinski, Victoria M;Quinn, Jennifer J
• 通讯作者: Quinn, Jennifer J