Name: extinction training during the reconsolidation window prevents recovery of fear
Uploaded: 2012-08-24T12:00:00
Description: Watch this Scientific Journal Video about Extinction Training During the Reconsolidation Window Prevents Recovery of Fear at JoVE.com

我们感谢D. Johnson和K. Doelling协助数据收集。我们也感谢M.-H.实验的协议，孟菲尔斯，J.勒社，Y. NIV和，M. MILAD建议。这项研究是由詹姆斯·麦克唐纳基金会和美国国立卫生研究院（NIH）资助R21 MH072279（EAP），国立卫生研究院资助R37 MH038774，P50 MH058911，RO1 MH046516和K05 MH067048（JEL），博士后奖学金NSERC，CIHR和AHFMR （M.-HM）和富布赖特和布拉瓦尼克奖（DS）。

概观在本协议中描述的研究中，我们进行了连续三天，三个实验组与主体之间的设计。第1天，所有受试者经历恐惧，他们学会区分两个线索，一个预测的冲击，另一种是不。第2天，所有受试者进行灭绝培训，但不同的方面会发生什么事先：两组收到提醒的提示，重新启动前的恐惧记忆消除训练，而第三组没有收到这样的提示。一组接收的提醒提示10分钟前灭绝，因此，他们经?...

<ol>
	<li>Pavlov, I. P., Anrep, G. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Reflexes. , (1927).</li><li>LeDoux, J. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Emotion+circuits+in+the+brain.">Emotion circuits in the brain.</a> Annual Review of Neuroscience. 23, 155-184 (2000).</li><li>Myers, K. M., Davis, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Behavioral+and+neural+analysis+of+extinction.">Behavioral and neural analysis of extinction.</a> Neuron. 36, 567-584 (2002).</li><li>Bouton, M. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Context,+ambiguity,+and+unlearning+:+sources+of+relapse+after+behavioral+extinction.">Context, ambiguity, and unlearning : sources of relapse after behavioral extinction.</a> Biological Psychiatry. 52, 976-986 (2002).</li><li>Nader, K., Schafe, G. E., LeDoux, J. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fear+memories+require+protein+synthesis+in+the+amygdala+for+reconsolidation+after+retrieval.">Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval.</a> Nature. 406, 722-726 (2000).</li><li>Nader, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Memory+traces+unbound.">Memory traces unbound.</a> Trends in Neuroscience. 26, 65-72 (2003).</li><li>Alberini, C. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mechanisms+of+memory+stabilization:+are+consolidation+and+reconsolidation+similar+or+distinct+processes.">Mechanisms of memory stabilization: are consolidation and reconsolidation similar or distinct processes.</a> Trends in Neuroscience. 28, 51-56 (2005).</li><li>Sara, S. J., Hars, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+memory+of+consolidation.">In memory of consolidation.</a> Learning and Memory. 13, 515-521 (2006).</li><li>Dudai, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reconsolidation:+the+advantage+of+being+refocused.">Reconsolidation: the advantage of being refocused.</a> Current Opinions in Neurobiology. 16, 174-178 (2006).</li><li>Schiller, D., Monfils, M. -. H., Raio, C. M., Johnson, D. C., LeDoux, J. E., Phelps, E. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Nature. 463, 49-54 (2010).</li><li>Monfils, M. -. H., Cowansage, K. K., Klann, E., LeDoux, J. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Extinction-reconsolidation+boundaries:+Key+to+persistent+attenuation+of+fear+memories.">Extinction-reconsolidation boundaries: Key to persistent attenuation of fear memories.</a> Science. 324, 951-955 (2009).</li><li>Brunet, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+post-+retrieval+propranololon+psychophysiologic+responding+during+subsequent+script-driven+traumatic+imagery+in+post-traumatic+stress+disorder.">Effect of post- retrieval propranololon psychophysiologic responding during subsequent script-driven traumatic imagery in post-traumatic stress disorder.</a> Journal of Psychiatric Research. 42, 503-506 (2008).</li><li>Kindt, M., Soeter, M., Vervliet, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Beyond+extinction:+erasing+human+fear+responses+and+preventing+the+return+of+fear.">Beyond extinction: erasing human fear responses and preventing the return of fear.</a> Nature Neuroscience. 12, 256-258 (2009).</li><li>Schiller, D., Phelps, E. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Does+reconsolidation+occur+in+humans.">Does reconsolidation occur in humans.</a> Frontiers in Behavioral Neuroscience. 5, 24 (2011).</li><li>Duvarci, S., Nader, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Characterization+of+fear+memory+reconsolidation.">Characterization of fear memory reconsolidation.</a> Journal of Neuroscience. 24, 9269-9275 (2004).</li><li>Walker, M. P., Brakefield, T., Hobson, J. A., Stickgold, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dissociable+stages+of+human+memory+consolidation+and+reconsolidation.">Dissociable stages of human memory consolidation and reconsolidation.</a> Nature. 425, 616-620 (2003).</li><li>Hupbach, A., Gomez, R., Hardt, O., Nadel, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reconsolidation+of+episodic+memories:+A+subtle+reminder+triggers+integration+of+new+information.">Reconsolidation of episodic memories: A subtle reminder triggers integration of new information.</a> Learning &#38; Memory. 14, 1-7 (2007).</li><li>Forcato, . <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reconsolidation+of+declarative+memory+in+humans.">Reconsolidation of declarative memory in humans.</a> Learning &#38; Memory. 14, 295-303 (2007).</li><li>McNally, G. P., Johanses, J. P., Blair, H. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Placing+prediction+into+the+fear+circuit.">Placing prediction into the fear circuit.</a> Trends in Cognitive Neuroscience. 34, 283-292 (2011).</li><li>Herry, C., Ferraguti, F., Singewald, N., Letzkus, J. J., Ehrlich, I., Luthi, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neural+circuits+of+fear+extinction.">Neural circuits of fear extinction.</a> European Journal of Neuroscience. 31, 599-612 (2010).</li><li>Phelps, E. A., Delgado, M. R., Nearing, K. I., LeDoux, J. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Extinction+learning+in+humans:+Role+of+the+amygdala+and+vmPFC.">Extinction learning in humans: Role of the amygdala and vmPFC.</a> Neuron. 43, 897-905 (2004).</li><li>Milad, M. R., Quirk, G. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neurons+in+the+medial+prefrontal+cortex+signal+memory+for+fear+extinction.">Neurons in the medial prefrontal cortex signal memory for fear extinction.</a> Nature. 420, 70-74 (2002).</li><li>Schiller, D., Levy, I., Niv, Y., LeDoux, J. E., Phelps, E. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=From+Fear+to+Safety+and+Back:+Reversal+of+Fear+in+the+Human+Brain.">From Fear to Safety and Back: Reversal of Fear in the Human Brain.</a> Journal of Neuroscience. 28, 11517-11525 (2008).</li><li>Schiller, D., Delgado, M. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Overlapping+neural+systems+mediating+extinction,+reversal+and+regulation+of+fear.">Overlapping neural systems mediating extinction, reversal and regulation of fear.</a> Trends in Cognitive Neuroscience. 14, 268-2627 (2010).</li><li>Esteves, F., Parra, C., Dimberg, U., Ohman, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Nonconscious+associative+learning:+Pavlovian+conditioning+of+skin+conductance+responses+to+masked+fear-relevant+facial+stimuli.">Nonconscious associative learning: Pavlovian conditioning of skin conductance responses to masked fear-relevant facial stimuli.</a> Psychophysiology. 31, 375-385 (1994).</li><li>Knight, D. C., Cheng, D. T., Smith, C. N., Stein, E. A., Helmstetter, F. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neural+Substrates+Mediating+Human+Delay+and+Trace+Fear+Conditioning.">Neural Substrates Mediating Human Delay and Trace Fear Conditioning.</a> The Journal of Neuroscience. 24, 218-228 (2004).</li><li>Venables, P. H., Christie, M. J., Martin, I., Venables, P. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Techniques+in+psychophysiology.">Techniques in psychophysiology.</a> Electrodermal activity. , 3-67 (1980).</li></ol>

我们这里介绍的协议，可以创建一个简单的恐惧厌恶的结果搭配一个中性刺激的响应。一天后，我们恢复了恐惧记忆，以触发其再巩固。在这个阶段，我们诱导干扰的形式灭绝训练。要验证灭绝会影响再巩固我们使用了两个对照组。一组接受没有提醒试验引发的再固结灭绝，而另一组经历了提醒的试验，然后进行灭绝的再固结窗口外。然后，我们测量了，在第二​​天，无论存储器自发收回或是?...

extinction training during the reconsolidation window prevents recovery of fear

恐惧是不适应的，持续时长后，情况已变得安全。因此，关键是开发一种方法，坚持防止返回的恐惧。巴甫洛夫恐惧调节范式通常是创建一个受控，新的恐惧在实验室协会。配对后无害的刺激（条件刺激，CS）与厌恶的结果（无条件刺激，美国），我们就可以引起恐惧反应（条件反射，或CR）呈现的刺激1,2。担心的是一旦收购，它可以减少使用灭绝训练，条件刺激重复出现，直到怕是没有厌恶的结果不再对3。这种抑制作用的学习创造一个新的，安全的CS表示，竞争的表达与原来的恐惧记忆4。虽然的灭绝是有效抑制恐惧，它不是永久性的。恐惧可以自发地追随着时间的推移。暴露于压力或返回的背景下，最初的学习也可能导致恐惧再度出现3,4。 我们的协议针对的的再固结窗口，修改情感记忆更持久的方式解决了过渡性质的灭绝。充足的证据表明，重新激活合并存储器，它返回到一个不稳定的状态，在此期间，存储器是再次易受干扰5-9。这一机会之窗打开后不久，激活和关闭约6小时后5,11,16，尽管这可能取决于的实力和存储器15岁。使新的信息纳入原有的记忆痕迹，内存可能会被更新，，因为它reconsolidates 10,11。涉及非人类的动物研究已经成功地阻止恐惧记忆的表达，通过引入药理内再操作整合的窗口，但是，大多数剂是对人体有毒的或使用时，在人类研究中12-14显示模棱两可的效果。我们的协议解决了这些难题提供了一个有效的，但非侵入性的，操纵行为，是对人类安全的。 提示的恐惧记忆检索的灭绝之前，我们基本上是触发再巩固过程，使新的安全信息（ 例如 ，消光）被纳入恐惧记忆仍然容易受到干扰。最近的一项研究在大鼠采用这种行为的操作已成功阻止恐惧记忆，用这些时间参数11。进一步的研究表明，在人类引入新的信息后，以前综合电机16，短暂的17，或声明的18记忆的检索干扰与原来的记忆痕迹14。下面我们概述了一种新的亲tocol用来阻止人类的恐惧恢复。

Watch this Scientific Journal Video about Extinction Training During the Reconsolidation Window Prevents Recovery of Fear at JoVE.com

Extinction Training During the Reconsolidation Window Prevents Recovery of Fear

条件性恐惧可以减少通过抑制过程的灭绝，但可以重新浮现根据条件，如通过时间或接触应力。我们的协议防止恐惧复苏过程中引入灭绝的的再固结窗口（重新存储阶段的恢复了记忆），提出了一种新的方式。

灭绝培训在彭兰霞窗口无法还原的恐惧

Fear is maladaptive when it persists long after circumstances have become safe. It is therefore crucial to develop an approach that persistently prevents ...

Research

JoVE Journal

Neuroscience

Human Fear Conditioning Conducted in Full Immersion 3-Dimensional Virtual Reality

人类的恐惧充分浸泡三维虚拟现实中进行的空调

Fear conditioning is a widely used paradigm in non-human animal research to investigate the neural mechanisms underlying fear and anxiety. A major ...

科研

神经科学

Intravital Microscopy of the Mouse Brain Microcirculation using a Closed Cranial Window

活体鼠脑微循环显微镜使用一个封闭的颅窗口

This experimental model was designed to assess the mouse pial microcirculation during acute and chronic, physiological and pathophysiological hemodynamic, ...

Investigating the Neural Mechanisms of Aware and Unaware Fear Memory with fMRI

调查的意识到，不知道用功能磁共振成像的恐惧记忆的神经机制

Pavlovian fear conditioning is often used in combination with functional magnetic resonance imaging (fMRI) in humans to investigate the neural substrates ...

Surgical Method for Virally Mediated Gene Delivery to the Mouse Inner Ear through the Round Window Membrane

通过圆窗膜病毒介导的基因传递给鼠标内耳手术方法

Gene therapy, used to achieve functional recovery from sensorineural deafness, promises to grant better understanding of the underlying molecular and ...

Ex Vivo Optogenetic Dissection of Fear Circuits in Brain Slices

Ex Vivo Optogenetic Dissection of Fear Circuits in Brain Slices

在脑片恐惧电路体外光遗传学解剖

Optogenetic approaches are now widely used to study the function of neural populations and circuits by combining targeted expression of light-activated ...

Preparation of Acute Brain Slices Using an Optimized N-Methyl-D-glucamine Protective Recovery Method

Preparation of Acute Brain Slices Using an Optimized N-Methyl-D-glucamine Protective Recovery Method

用优化的n-甲基 d-葡乙胺保护恢复法制备急性脑切片

This protocol is a practical guide to the N-methyl-D-glucamine (NMDG) protective recovery method of brain slice preparation. Numerous recent studies have ...

A Protocol for the Administration of Real-Time fMRI Neurofeedback Training

实时 fMRI 神经训练管理协议

Neurologic disorders are characterized by abnormal cellular-, molecular-, and circuit-level functions in the brain. New methods to induce and control ...

A Microbiomechanical System for Studying Varicosity Formation and Recovery in Central Neuron Axons

中枢神经元轴突静脉曲张形成和恢复的 Microbiomechanical 系统研究

Axonal varicosities are enlarged structures along the shafts of axons with a high degree of heterogeneity. They are present not only in brains with ...

Laminectomy and Spinal Cord Window Implantation in the Mouse

拉米内切手术和脊髓窗口植入小鼠

This protocol describes a method for spinal cord laminectomy and glass window implantation for in vivo imaging of the mouse spinal cord. An integrated ...

Electrophoretic Delivery of &#x3B3;-aminobutyric Acid (GABA) into Epileptic Focus Prevents Seizures in Mice

Electrophoretic Delivery of &#947;-aminobutyric Acid GABA into Epileptic Focus Prevents Seizures in Mice

将γ-氨基丁酸 (GABA) 电泳到癫痫焦点中进行, 防止小鼠癫痫发作

Epilepsy is a group of neurological disorders which affects millions of people worldwide. Although treatment with medication is helpful in 70% of the ...