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）： 在战斗和服务之后，退伍军人患有焦虑症的风险增加，尤其是创伤后应激障碍（PTSD）。风险被概念化为影响脆弱性与环境压力源相互作用，应对策略和支持的可用性的遗传和表观遗传因素。面对厌恶刺激，概念和记忆，避免，获得的行为和情感调整，追溯了焦虑症的过程，并且是PTSD的关键组成部分。我们的基础科学研究计划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Wistar-Kyoto大鼠的压力敏感，并且比近代的Sprague-Dawley大鼠更快地获得主动回避反应。我们已经确定了一个关键特征，可以解释WKY大鼠更快地获取的一种来源。在非威胁期间存在明确提示的存在，该提示可能被编码为显式信号安全信号，也可以被视为额外的厌恶刺激。因此，AIM 1将确定为什么在非威胁性审判间隔期间提出的显式视觉提示有助于避免WKY大鼠的回避习得。 AIM 2将揭示脆弱性的神经生物学来源，重点是内侧前额叶皮层的各个方面（输液，前骨和前扣带回皮层），该区域已知，以评估威胁与安全和回避学习的区域。因此，该领域还涉及引起焦虑症。因此，我们的计划旨在暴露出一种焦虑症和PTSD发展的风险来源。对于易受伤害的人，安全与威胁的处理升级并升级为耐灭绝和治疗的病理水平。抵消神经生物学过程，从而增强了内侧前额叶皮层中威胁和安全性的加工，将使避免避免到可耐受的水平。

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