National Centre for Biological Sciences, Bangalore, India.
Centre for Brain Development and Repair, Institute for Stem Cell Biology and Regenerative Medicine, Bangalore, India.
Elife. 2018 Aug 13;7:e35450. doi: 10.7554/eLife.35450.
Stress is known to exert its detrimental effects not only by enhancing fear, but also by impairing its extinction. However, in earlier studies stress exposure preceded both processes. Thus, compared to unstressed animals, stressed animals had to extinguish fear memories that were strengthened by prior exposure to stress. Here, we dissociate the two processes to examine if stress specifically impairs the acquisition and recall of fear extinction. Strikingly, when fear memories were formed before stress exposure, thereby allowing animals to initiate extinction from comparable levels of fear, recall of fear extinction was unaffected. Despite this, we observed a persistent increase in theta activity in the BLA. Theta activity in the mPFC, by contrast, was normal. Stress also disrupted mPFC-BLA theta-frequency synchrony and directional coupling. Thus, in the absence of the fear-enhancing effects of stress, the expression of fear during and after extinction reflects normal regulation of theta activity in the mPFC, not theta hyperactivity in the amygdala.
压力不仅通过增强恐惧,而且通过损害其消退来发挥其有害作用。然而,在早期的研究中,压力暴露先于这两个过程。因此,与未受压力的动物相比,受到压力的动物必须消除由于先前暴露于压力而增强的恐惧记忆。在这里,我们将这两个过程分开,以检查压力是否专门损害了恐惧消退的获得和回忆。令人惊讶的是,当恐惧记忆在压力暴露之前形成,从而允许动物从可比的恐惧水平开始消退时,恐惧消退的回忆不受影响。尽管如此,我们观察到 BLA 中的θ活动持续增加。相比之下,mPFC 中的θ活动是正常的。压力还破坏了 mPFC-BLAθ频率同步和方向耦合。因此,在没有压力增强恐惧作用的情况下,在消退期间和之后表达的恐惧反映了 mPFC 中θ活动的正常调节,而不是杏仁核中的θ过度活跃。