Department of Psychology and Neuroscience, University of Colorado, Boulder, Colorado 80309-0345, USA.
Learn Mem. 2010 Nov 1;17(11):591-9. doi: 10.1101/lm.1920810. Print 2010 Nov.
Activation of the infralimbic region (IL) of the medial prefrontal cortex (mPFC) reduces conditioned fear in a variety of situations, and the IL is thought to play an important role in the extinction of conditioned fear. Here we report a series of experiments using contextual fear conditioning in which the IL is activated with the GABAa antagonist picrotoxin (Ptx) during a single extinction session in the fear context. We investigate the impact of this manipulation on subsequent extinction sessions in which Ptx is no longer present. First, we demonstrate that a single treatment with intra-IL Ptx administered in a conditioned fear context greatly accelerates the rate of extinction on the following days. Importantly, IL-Ptx also enhances extinction to a different fear context than the one in which IL-Ptx was administered. Thus, IL-Ptx primes extinction learning regardless of the fear context in which the IL was initially activated. Second, activation of the IL must occur in conjunction with a fear context in order to enhance extinction; the extinction enhancing effect is not observable if IL-Ptx is administered in a neutral context. Finally, this extinction enhancing effect is specific to the IL for it does not occur if Ptx is injected into the prelimbic region (PL) of the mPFC. The results indicate a novel persisting control of fear induced by activation of the IL and suggest that IL activation induces changes in extinction-related circuitry that prime extinction learning.
内侧前额叶皮层（mPFC）的下边缘区域（IL）的激活可减少各种情况下的条件性恐惧，并且 IL 被认为在条件性恐惧的消除中发挥重要作用。在这里，我们报告了一系列使用情境恐惧条件反射的实验，其中在恐惧情境中的单次消退过程中，用 GABAa 拮抗剂印防己毒素（Ptx）激活 IL。我们研究了这种操作对随后不再存在 Ptx 的消退过程的影响。首先，我们证明，在条件恐惧环境中单次给予 IL 内 Ptx 处理可大大加速随后几天的消退速度。重要的是，IL-Ptx 还增强了与 Ptx 给药的恐惧环境不同的恐惧环境的消退。因此，IL-Ptx 引发了无论最初激活的 IL 处于何种恐惧环境下的消退学习。其次，IL 的激活必须与恐惧环境同时发生才能增强消退；如果在中性环境中给予 IL-Ptx，则不会观察到增强消退的效果。最后，这种增强消退的效果是特定于 IL 的，如果将 Ptx 注射到 mPFC 的前扣带皮层（PL）中，则不会发生这种情况。结果表明，IL 的激活引起了一种新的持久的恐惧控制，并表明 IL 激活诱导了与消退相关的电路的变化，从而引发了消退学习。
