Active avoidance learning requires prefrontal suppression of amygdala-mediated defensive reactions.
Active avoidance learning requires prefrontal suppression of amygdala-mediated defensive reactions.
复制标题
主动避免学习需要前额叶抑制杏仁核介导的防御反应。
DOI：
10.1523/jneurosci.2596-12.2013
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发表时间：
2013-02-27
期刊：
影响因子：
--
通讯作者：
LeDoux JE
中科院分区：
文献类型：
--
作者：
Moscarello JM;LeDoux JE
信号主动回避（Signaled active avoidance，AA）范式训练受试者通过在条件提示的呈现过程中执行习得行为来防止厌恶性结果。这种复杂形式的条件反射涉及巴甫洛夫和工具性成分，它们产生竞争性的行为反应，必须使受试者成功地避免厌恶刺激。在大鼠信号AA范式中，我们检验了AA训练的工具成分招募边缘下前额叶皮层（infraalimbic prefrontal cortex，ilPFC）抑制中央杏仁核（central amygdala，CeA）介导的巴甫洛夫反应的假说。训练前病变的ilPFC增加条件冻结，同时导致相应的减少回避;病变的CeA产生相反的效果，减少冻结和促进回避行为。药理学失活实验表明，ilPFC是相关的收购和AA学习的表达阶段。失活实验还表明，AA产生的ilPFC介导的巴甫洛夫反应的减少，超出了培训的背景下，即使当条件刺激是在一个环境中，不允许回避反应。最后，注射蛋白质合成抑制剂到ilPFC或CeA受损或促进AA，分别表明，回避训练产生两个相反的记忆痕迹，在这些地区。这些数据支持一个模型，在该模型中，AA学习招募ilPFC来抑制CeA介导的防御行为，从而导致在整个环境中普遍存在的冻结的强烈抑制。因此，ilPFC功能作为一个抑制界面，允许工具控制一个令人厌恶的结果，以减弱表达冻结和其他反应条件的威胁。
Signaled active avoidance (AA) paradigms train subjects to prevent an aversive outcome by performing a learned behavior during the presentation of a conditioned cue. This complex form of conditioning involves Pavlovian and instrumental components, which produce competing behavioral responses that must be reconciled for the subject to successfully avoid an aversive stimulus. In signaled AA paradigm for rat, we tested the hypothesis that the instrumental component of AA training recruits infralimbic prefrontal cortex (ilPFC) to inhibit central amygdala (CeA) mediated Pavlovian reactions. Pre-training lesions of ilPFC increased conditioned freezing while causing a corresponding decrease in avoidance; lesions of CeA produced opposite effects, reducing freezing and facilitating avoidance behavior. Pharmacological inactivation experiments demonstrated that ilPFC is relevant to both acquisition and expression phases of AA learning. Inactivation experiments also revealed that AA produces an ilPFC-mediated diminution of Pavlovian reactions that extends beyond the training context, even when the conditioned stimulus is presented in an environment that does not allow the avoidance response. Finally, injection of a protein synthesis inhibitor into either ilPFC or CeA impaired or facilitated AA, respectively, showing that avoidance training produces two opposing memory traces in these regions. These data support a model in which AA learning recruits ilPFC to inhibit CeA-mediated defense behaviors, leading to a robust suppression of freezing that generalizes across environments. Thus, ilPFC functions as an inhibitory interface, allowing instrumental control over an aversive outcome to attenuate the expression of freezing and other reactions to conditioned threat.