Spreading depolarization (SD), a self-propagating wave of near-complete breakdown of the transmembrane ion gradients with water influx, regularly occurs in traumatized human brain. Here, we investigated long-term neurobehavioral consequences of injury-triggered SDs. Recently, we revealed that SD is reliably triggered by micro-injury of the amygdala, a key brain structure involved in fear processing. Using the classical Pavlovian fear conditioning paradigm, we investigated effects of the post-retrieval amygdala micro-injury and associated SD on fear memory in rats. We found that neither SD nor micro-injury alone affect fear response 24 h later but profoundly change it in subsequent extinction phase. If bilateral injury of the amygdala did not induce SD, fear extinction was severely impaired, while conditioned fear in rats with the identical amygdala injury triggering SD was successfully extinguished similarly to naïve rats. Our study provides first experimental evidence for involvement of injury-induced SD in extinction of traumatic fear memory.

扩散去极化 (SD) 是跨膜离子梯度随水流入而几乎完全分解的自传播波，经常发生在受创伤的人脑中。在这里，我们调查了损伤触发的 SD 的长期神经行为后果。最近，我们揭示了 SD 是由杏仁核的微损伤可靠地触发的，杏仁核是参与恐惧处理的关键大脑结构。使用经典的巴甫洛夫恐惧条件范式，我们研究了检索后杏仁核微损伤和相关 SD 对大鼠恐惧记忆的影响。我们发现，SD 和微损伤都不会单独影响 24 小时后的恐惧反应，但会在随后的消退阶段深刻地改变它。如果杏仁核的双侧损伤没有引起 SD，恐惧消退严重受损，而同样的杏仁核损伤触发 SD 的大鼠的条件性恐惧与幼稚大鼠类似地被成功消除。我们的研究为损伤诱发的 SD 参与创伤性恐惧记忆的消退提供了第一个实验证据。