Neural mechanisms of extinction-resistant avoidance behavior

抗灭绝回避行为的神经机制

• 批准号: 8394591
• 负责人: Kevin D. Beck
• 金额: --
• 依托单位: VA NEW JERSEY HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8394591
• 关键词: Amygdaloid structure; Animal Model; Animals; Anterior; Anxiety Disorders; Area; Arousal; Association Learning; Attention; Aversive Stimulus; Avoidance Learning; Basic Science; Behavior; Behavioral; Cells; Characteristics; Cognitive; Cues; Development; Disinhibition; Environment; Epigenetic Process; Excision; Exhibits; Exposure to; Extinction (Psychology); Fright; Genetic; Hippocampus (Brain); Immunohistochemistry; Inbred WKY Rats; Inbreeding; Individual; Label; Learning; Light; Limbic System; Localized Lesion; Measures; Medial; Memory; Mental Health; Military Personnel; Neurobiology; Neurons; Post-Traumatic Stress Disorders; Prefrontal Cortex; Process; Rattus; Reaction; Regulation; Research; Resistance; Risk; Role; Safety; Services; Shock; Signal Transduction; Source; Sprague-Dawley Rats; Stimulus; Stress; Symptoms; Techniques; Temperament; Testing; Thalamic structure; Training; Veterans; Visual; avoidance behavior; cell type; cingulate cortex; combat; coping; design; emotional adjustment; environmental stressor; inhibitor/antagonist; meetings; neuromechanism; programs; relating to nervous system; response; stressor

DESCRIPTION (provided by applicant): Veterans are at increased risk for developing anxiety disorders - particularly posttraumatic stress disorder (PTSD) -- in the aftermath of combat and service. Risk is conceptualized as genetic and epigenetic factors influencing vulnerability interacting with environmental stressors, coping strategies and availability of support. Avoidance, acquired behavioral and emotional adjustments in the face of aversive stimuli, concepts and memories, traces the course of anxiety disorders and is a critical component of PTSD. Our basic science research program is developing an animal model for understanding the role of vulnerability in avoidance learning. Inbred Wistar-Kyoto rats are stress sensitive and acquire active avoidance response faster and to a higher degree than outbred Sprague-Dawley rats. We have identified a critical feature that may explain one source of faster acquisition in WKY rats; the presence of an explicit cue during periods of non-threat, which may be encoded as an explicit signal safety signal or perceived as an additional aversive stimulus. Accordingly, AIM 1 will determine why the explicit visual cue presented during the non-threat inter-trial interval facilitates avoidance acquisition in WKY rats. AIM 2 will expose the neurobiological source of the vulnerability focusing on aspects of the medial prefrontal cortex (infralimbic, prelimbic, and anterior cingulate cortices), areas known to assess threat versus safety and avoidance learning. Consequently, this area is also implicated in causing anxiety disorders. Thus, our program is designed to expose one source of risk for the development of anxiety disorders and PTSD in particular. For the vulnerable, the processing of safety versus threat escalates normal avoidance and coping to a pathological level which is resistant to extinction and treatment. Counteracting the neurobiological processes sub-serving enhanced processing of threat and safety in the medial prefrontal cortex will reduce avoidance to tolerable levels.

描述（由申请人提供）： 退伍军人在战斗和服役后患焦虑症的风险增加，特别是创伤后应激障碍（PTSD）。风险的概念是影响脆弱性的遗传和表观遗传因素，与环境压力、应对策略和支持的可用性相互作用。回避，在面对厌恶性刺激，概念和记忆时获得的行为和情绪调整，追溯了焦虑症的过程，是PTSD的关键组成部分。我们的基础科学研究项目正在开发一种动物模型，以了解脆弱性在回避学习中的作用。近交系Wistar-Kyoto大鼠是应激敏感的，并且比远交系Sprague-Dawley大鼠更快地获得主动回避反应，并且获得的程度更高。我们已经确定了一个关键的功能，可以解释一个来源的更快的收购WKY大鼠;在非威胁期间，这可能是编码为一个明确的信号安全信号或感知为一个额外的厌恶刺激的一个明确的线索的存在。因此，AIM 1将确定为什么在非威胁试验间隔期间呈现的明确视觉提示有助于WKY大鼠的回避获取。AIM 2将揭示脆弱性的神经生物学来源，重点关注内侧前额叶皮层（边缘下、边缘前和前扣带皮层），这些区域已知用于评估威胁与安全和回避学习。因此，这个区域也与引起焦虑症有关。因此，我们的计划旨在揭示焦虑症和创伤后应激障碍的风险来源之一。对于脆弱者来说，安全与威胁的处理将正常的回避和应对升级到一个病理水平，这个水平抵抗灭绝和治疗。在内侧前额叶皮层中，抵消辅助增强威胁和安全处理的神经生物学过程将使回避减少到可容忍的水平。

项目成果

Using signals associated with safety in avoidance learning: computational model of sex differences.

在回避学习中使用与安全相关的信号：性别差异的计算模型。

• DOI: 10.7717/peerj.1081
• 发表时间: 2015
• 期刊: PeerJ
• 影响因子: 2.7
• 作者: Radell,MilenL;Beck,KevinD;Pang,KevinCH;Myers,CatherineE
• 通讯作者: Myers,CatherineE

Activation of extracellular signal-regulated kinase (ERK) and ΔFosB in emotion-associated neural circuitry after asymptotic levels of active avoidance behavior are attained.

在达到主动回避行为的渐近水平后，情绪相关神经回路中的细胞外信号调节激酶 (ERK) 和 ΔFosB 被激活。

• DOI: 10.1016/j.brainresbull.2013.07.004
• 发表时间: 2013
• 期刊: Brain research bulletin
• 影响因子: 3.8
• 作者: Perrotti,LindaI;Dennis,TorryS;Jiao,Xilu;Servatius,RichardJ;Pang,KevinCH;Beck,KevinD
• 通讯作者: Beck,KevinD

Absence of "Warm-Up" during Active Avoidance Learning in a Rat Model of Anxiety Vulnerability: Insights from Computational Modeling.

焦虑脆弱性大鼠模型中主动回避学习期间缺乏“热身”：来自计算模型的见解。

• DOI: 10.3389/fnbeh.2014.00283
• 发表时间: 2014
• 期刊: Frontiers in behavioral neuroscience
• 影响因子: 3
• 作者: Myers,CatherineE;Smith,IanM;Servatius,RichardJ;Beck,KevinD
• 通讯作者: Beck,KevinD