Enhanced discriminative aversive learning and amygdala responsivity in 5-HT transporter mutant mice.
Enhanced discriminative aversive learning and amygdala responsivity in 5-HT transporter mutant mice.
复制标题
5-HT 转运蛋白突变小鼠的辨别厌恶学习和杏仁核反应能力增强。
DOI：
10.1038/s41398-019-0476-8
复制
发表时间：
2019
影响因子：
6.8
通讯作者：
Lima J
中科院分区：
文献类型：
--
作者：
Lima J
人类5-羟色胺转运体（5-HTT）的遗传变异与恐惧学习的改变有关，但数据不一致，机制也不清楚。本研究调查了5-HTT基因敲除（KO）小鼠的条件厌恶学习，同时记录杏仁核的神经网络活动（θ振荡）和血液动力学反应（组织氧输送），杏仁核是形成恐惧记忆所必需的大脑区域。条件性厌恶学习测量使用的歧视学习任务，其中一个听觉线索与脚电击配对，而第二个听觉线索没有。与野生型小鼠相比，5-HTTKO小鼠表现出更快的辨别学习。这种效应与更强的θ频率振荡和杏仁核中更大的血流动力学变化有关，以响应情感相关的线索和无条件的足部电击刺激。此外，血流动力学反应的非条件刺激预测的行为歧视性能的第二天。野生型小鼠的急性药理学5-HTT阻断产生了类似的效果，在一定程度上，在恐惧条件反射期间给予西酞普兰增强了恐惧记忆回忆。总的来说，我们的数据表明，5-HTT功能的丧失增强了杏仁核对厌恶事件的反应性，并促进了对情感相关线索的学习。
Genetic variation in the human serotonin transporter (5-HTT) has been linked to altered fear learning but the data are inconsistent and the mechanism is unclear. The present study investigated conditioned aversive learning in 5-HTT knockout (KO) mice while simultaneously recording neural network activity (theta oscillations) and hemodynamic responses (tissue oxygen delivery) from the amygdala, a brain region necessary for forming fearful memories. Conditioned aversive learning was measured using a discrimination learning task in which one auditory cue was paired with foot-shock, whereas a second auditory cue was not. Compared with wild-type mice, 5-HTTKO mice exhibited faster discrimination learning. This effect was associated with stronger theta frequency oscillations and greater hemodynamic changes in the amygdala in response to both the emotionally relevant cues and the unconditioned foot-shock stimulus. Furthermore, hemodynamic responses to the unconditioned stimulus predicted behavioral discrimination performance the following day. Acute pharmacological 5-HTT blockade in wild-type mice produced a similar effect, to the extent that administration of citalopram during the fear conditioning sessions enhanced fear memory recall. Collectively, our data argue that loss of 5-HTT function enhances amygdala responsivity to aversive events and facilitates learning for emotionally relevant cues.