Graduate Program in Neuroscience, Universidade Federal de Santa Catarina (UFSC), Florianópolis, SC, Brazil.
Center for Applied Neuroscience, Hospital Universitário (HU), UFSC, Florianópolis, SC, Brazil.
Mol Psychiatry. 2021 Dec;26(12):7257-7269. doi: 10.1038/s41380-021-01203-0. Epub 2021 Jul 27.
We demonstrate that the rate of extracellular signal-related kinase phosphorylation (P-ERK1,2/Total-ERK1,2) in the amygdala is negatively and independently associated with anxiety symptoms in 23 consecutive patients with drug-resistant mesial temporal lobe epilepsy that was surgically treated. In naive Wistar rats, the P-ERK1,2/Total-ERK1,2 ratio in the amygdala correlates negatively with innate anxiety-related behavior on the elevated plus maze (n = 20) but positively with expression of defensive-learned behavior (i.e., freezing) on Pavlovian aversive (fear) conditioning (n = 29). The microinfusion of ERK1/2 inhibitor (FR180204, n = 8-13/group) or MEK inhibitor (U0126, n = 8-9/group) into the basolateral amygdala did not affect anxiety-related behavior but impaired the evocation (anticipation) of conditioned-defensive behavior (n = 9-11/group). In conclusion, the P-ERK1,2/Total-ERK1,2 ratio in the amygdala predicts anxiety in humans and the innate anxiety- and conditioned freezing behaviors in rats. However, the ERK1/2 in the basolateral AMY is only required for the expression of defensive-learned behavior. These results support a dissociate ERK-dependent mechanism in the amygdala between innate anxiety-like responses and the anticipation of learned-defensive behavior. These findings have implications for understanding highly prevalent psychiatric disorders related to the defensive circuit manifested by anxiety and fear. HIGHLIGHTS: The P-ERK1,2/Total-ERK1,2 ratio in the amygdala (AMY) correlates negatively with anxiety symptoms in patients with mesial temporal lobe epilepsy. The P-ERK1,2/Total-ERK1,2 in the amygdala correlates negatively with the anxiety-like behavior and positively with freezing-learned behavior in naive rats. ERK1,2 in the basolateral amygdala is required for learned-defensive but not for the anxiety-like behavior expression in rats.
我们证明，在 23 例接受手术治疗的耐药性内侧颞叶癫痫患者中，杏仁核细胞外信号相关激酶磷酸化（P-ERK1,2/总-ERK1,2）的速率与焦虑症状呈负相关且独立相关。在未接受处理的 Wistar 大鼠中，杏仁核中的 P-ERK1,2/总-ERK1,2 比率与高架十字迷宫上的先天焦虑相关行为呈负相关（n=20），但与条件性回避（恐惧）条件反射中的防御性习得行为（即冻结）呈正相关（n=29）。ERK1/2 抑制剂（FR180204，n=8-13/组）或 MEK 抑制剂（U0126，n=8-9/组）微灌流至基底外侧杏仁核不会影响焦虑相关行为，但会损害条件防御行为的唤起（预期）（n=9-11/组）。总之，杏仁核中的 P-ERK1,2/总-ERK1,2 比率可预测人类的焦虑以及大鼠的先天焦虑和条件性冻结行为。然而，基底外侧 AMY 中的 ERK1/2 仅用于表达防御性习得行为。这些结果支持了杏仁核中 ERK 依赖性机制在先天焦虑样反应和对习得防御行为的预期之间的分离。这些发现对于理解与焦虑和恐惧表现的防御回路相关的高度流行的精神疾病具有重要意义。要点：杏仁核（AMY）中的 P-ERK1,2/总-ERK1,2 比率与内侧颞叶癫痫患者的焦虑症状呈负相关。杏仁核中的 P-ERK1,2/总-ERK1,2 与未接受处理的大鼠的焦虑样行为呈负相关，与冻结习得行为呈正相关。基底外侧杏仁核中的 ERK1,2 对于习得性防御行为是必需的，但对于大鼠的焦虑样行为表达不是必需的。
