Brain Mind Institute, School of Life Sciences, EPFL, Lausanne, Switzerland.
Adv Neurobiol. 2024;38:149-161. doi: 10.1007/978-3-031-62983-9_9.
Fear attenuation is an etiologically relevant process for animal survival, since once acquired information needs to be continuously updated in the face of changing environmental contingencies. Thus, when situations are encountered that were originally perceived as fearful but are no longer so, fear must be attenuated, otherwise, it risks becoming maladaptive. But what happens to the original memory trace of fear during fear attenuation? In this chapter, we review the studies that have started to approach this question from an engram perspective. We find evidence pointing to both the original memory trace of fear being suppressed, as well as it being updated towards safety. These seemingly conflicting results reflect a well-established dichotomy in the field of fear memory attenuation, namely whether fear attenuation is mediated by an inhibitory mechanism that suppresses fear expression, called extinction, or by an updating mechanism that allows the fear memory to reconsolidate in a different form, called reconsolidation-updating. Which of these scenarios takes the upper hand is ultimately influenced by the behavioral paradigms used to induce fear attenuation, but is an important area for further study as the precise cell populations underlying fear attenuation and the molecular mechanisms therein can now be understood at unprecedented resolution.
恐惧衰减是动物生存的一个与病因相关的过程,因为一旦获得的信息需要在面对不断变化的环境时不断更新。因此,当遇到最初被感知为恐惧但不再如此的情况时,必须减弱恐惧,否则,它可能变得适应不良。但是,在恐惧衰减过程中,原始的恐惧记忆痕迹会发生什么变化呢?在这一章中,我们从记忆痕迹的角度回顾了一些开始研究这个问题的研究。我们发现的证据表明,恐惧的原始记忆痕迹既被抑制,也朝着安全的方向更新。这些看似矛盾的结果反映了恐惧记忆衰减领域中一个既定的二分法,即恐惧衰减是由抑制性机制介导的,该机制抑制恐惧表达,称为消退,还是由更新机制介导的,该机制允许恐惧记忆以不同的形式重新巩固,称为再巩固更新。哪种情况占上风最终取决于用于诱导恐惧衰减的行为范式,但这是一个进一步研究的重要领域,因为现在可以以前所未有的分辨率理解恐惧衰减背后的精确细胞群体及其分子机制。
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