条件性恐惧消退过程中大鼠边缘下区突触素和神经细胞黏附分子的变化

目的 研究条件性恐惧消退过程中,内侧前额叶边缘下区突触素、神经细胞黏附分子免疫反应阳性物质的动态变化.方法 将72只成年雄性SD大鼠随机分为自然消退组(条件恐惧建立后不进行消退训练,n=24)、立即消退组(条件恐惧建立后15 min进行消退训练,n=24)和24 h消退组(条件恐惧建立后24 h进行消退训练,n=24),采用声音提示的足底电击建立大鼠恐惧记忆,然后单独给声音信号进行恐惧消退训练.在条件恐惧建立后(立即消退组和24 h消退组在消退训练后)第1,3,7和20天分别进行消退保持测验,并在各时间点取边缘下区标本进行突触素、神经细胞黏附分子的免疫组化研究.结果 在恐惧消退过程中,(1)3组大鼠消退成绩整体呈上升趋势,其中24h消退组在第7天最高[(79±17)%],且在各时间点消退保持成绩最好(P<0.01);(2)3组大鼠边缘下区突触素免疫反应阳性物质逐渐增加而后减少,第7天最高(P<0.01);(3)3组大鼠边缘下区神经细胞黏附分子免疫反应阳性物质逐渐增加,其中自然消退组在消退后第3天最高,其余2组在消退后第7天最高(P<0.01).结论 恐惧消退后3～7 d,边缘下区突触可塑性相关物质水平能较好地反映消退记忆的保持情况.

Change of synaptophysin and neural cell adhesion molecule immunoreactive positive substances in infra-limbic cortex after fear extinction

Objective To observe the change of synaptophysin and neural cell adhesion molecule (NCAM) immunoreactive positive substances in infra-limbic cortex (IL) of medial prefrontal cortex (mPFC) after fear extinction. Methods After conditioned fear model was made, 72 male adult SD rats were randomly divided into natural-extinction group (n=24), immadlate-extinction group (n=24) and 24-hour-extinction group (n=24). Conditioned fear was established by tone paired foot shock. Rats were trained with only tone signal for fear extinction (fear extinction was performed in 15 minutes or 24 hours after establishment of conditioned fear). Extinction retention test, immunohistochemistry test of synaptophysin and NCAM were done at 1st, 3rd, 7th and 20th day after fear extinction. Results (1) Extinction retention scores were increased gradually and reached the peak in 24-hour-extinction group at 7th day after extinction. Extinction retention score was the best in 24-hour-extinction group as compared to the other two groups (P<0.01). (2) Synaptophysin and NCAM immunoreactive positive substances were increased gradually in all groups. Synaptophysin expression reached the highest level at 7th day then reduced (P<0.01). (3) NCAM expression reached the highest point at 3rd day in natural-extinction group, at 7th day in the other two groups (P<0.01). Conclusion It indicates that extinction retention score be correlated with the amount of plasticity-related synaptophysin and NCAM in infra-limbic cortex at 3-7th day after fear extinction. The level of plasticity-related substances in infra-limbic cortex could reflect the extent of extinction retention.