Cognitive Flexibility Training Improves Extinction Retention Memory and Enhances Cortical Dopamine With and Without Traumatic Stress Exposure
Cognitive Flexibility Training Improves Extinction Retention Memory and Enhances Cortical Dopamine With and Without Traumatic Stress Exposure
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DOI：
10.3389/fnbeh.2019.00024
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发表时间：
2019-03-01
影响因子：
3
通讯作者：
Liberzon, Israel
中科院分区：
文献类型：
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作者：
Chaby, Lauren E.;Karavidha, Klevis;Liberzon, Israel
压力暴露可以导致认知的持久变化，但某些个体特征，如认知灵活性，已被证明可以降低压力后认知变化的程度，持续时间或严重程度。压力和认知灵活性训练都通过调节单胺信号来影响决策。在这里，我们测试的作用认知灵活性训练，和高与低认知灵活性在个人层面上，在衰减应力引起的变化，记忆和单胺水平使用单一的长期压力（SPS）啮齿动物模型的创伤性应激雄性Sprague-Dawley大鼠。暴露于SPS可以提高对条件提示的恐惧反应（即，冻结）后，恐惧协会已被扑灭，称为赤字灭绝保留。这种缺陷被认为反映了创伤后应激障碍（PTSD）特征的背景处理障碍。在认知灵活性训练中，我们评估了认知技能的个体差异，并对大鼠进行了条件反射，以在其环境中有区别地使用线索。我们发现，认知灵活性训练，单独或随后的SPS曝光，加速灭绝学习和减少恐惧反应，随着时间的推移，在灭绝保持测试，与大鼠相比，没有给予认知灵活性训练。这些发现表明，认知灵活性训练可以改善有和没有创伤应激暴露的个体的上下文处理。在认知灵活性训练的逆转阶段的个人表现预测随后的上下文处理;具有高逆转性能的个人表现出更快的下降，在消光保留测试过程中的冻结反应。因此，高逆转性能预测随着时间的推移增强保留的灭绝学习，并表明认知灵活性训练可能是一种策略，以促进上下文处理。在维持认知灵活性和恐惧抑制至关重要的大脑区域，前边缘皮层（PLC），认知灵活性训练也持久地提高了多巴胺（DA）和去甲肾上腺素（NE）水平，在有和没有创伤应激暴露的动物中。相比之下，认知灵活性训练之前，创伤应激暴露降低水平的DA及其代谢产物在纹状体，一个区域调解反射决策。总的来说，我们的研究结果表明，认知灵活性训练可以通过增强消退保留（创伤的标志性认知效应）和前边缘DA（可以在不断变化的环境中保持灵活性）来提供持久的益处。
Stress exposure can cause lasting changes in cognition, but certain individual traits, such as cognitive flexibility, have been shown to reduce the degree, duration, or severity of cognitive changes following stress. Both stress and cognitive flexibility training affect decision making by modulating monoamine signaling. Here, we test the role cognitive flexibility training, and high vs. low cognitive flexibility at the individual level, in attenuating stress-induced changes in memory and monoamine levels using the single prolonged stress (SPS) rodent model of traumatic stress in male Sprague-Dawley rats. Exposure to SPS can heighten fear responses to conditioned cues (i.e., freezing) after a fear association has been extinguished, referred to as a deficit in extinction retention. This deficit is thought to reflect an impairment in context processing that is characteristic of posttraumatic stress disorder (PTSD). During a cognitive flexibility training we assessed individual variability in cognitive skills and conditioned rats to discriminately use cues in their environment. We found that cognitive flexibility training, alone or followed by SPS exposure, accelerated extinction learning and decreased fear responses over time during extinction retention testing, compared with rats not given cognitive flexibility training. These findings suggest that cognitive flexibility training may improve context processing in individuals with and without traumatic stress exposure. Individual performance during the reversal phase of the cognitive flexibility training predicted subsequent context processing; individuals with high reversal performance exhibited a faster decrease in freezing responses during extinction retention testing. Thus, high reversal performance predicted enhanced retention of extinction learning over time and suggests that cognitive flexibility training may be a strategy to promote context processing. In a brain region vital for maintaining cognitive flexibility and fear suppression, the prelimbic cortex (PLC), cognitive flexibility training also lastingly enhanced dopamine (DA) and norepinephrine (NE) levels, in animals with and without traumatic stress exposure. In contrast, cognitive flexibility training prior to traumatic stress exposure decreased levels of DA and its metabolites in the striatum, a region mediating reflexive decision making. Overall, our results suggest that cognitive flexibility training can provide lasting benefits by enhancing extinction retention, a hallmark cognitive effect of trauma, and prelimbic DA, which can maintain flexibility across changing contexts.