Piao Chengji, Deng Xiaofei, Wang Xingyue, Yuan Yiran, Liu Zhengkui, Liang Jing
CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China; Graduate University of Chinese Academy of Science, Beijing 100049, China; Sino-Danish Center for Education and Research, Beijing 100190, China.
CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China; Graduate University of Chinese Academy of Science, Beijing 100049, China.
Behav Brain Res. 2017 Jan 15;317:16-26. doi: 10.1016/j.bbr.2016.09.017. Epub 2016 Sep 8.
The medial prefrontal cortex (mPFC) and its output area, the nucleus accumbens (NAc), are implicated in mediating attentional set-shifting. Patients with posttraumatic stress disorder (PTSD) exhibit difficulties in the disengagement of attention from traumatic cues, which is associated with impairments in set-shifting ability. However, unknown is whether alterations in corticostriatal function underlie deficits in this behavioral flexibility in individuals with PTSD. An animal model of single prolonged stress (SPS) has been partially validated as a model for PTSD, in which SPS rats recapitulate the pathophysiological abnormalities and behavioral characteristics of PTSD. In the present study, we firstly found that exposure to SPS impaired the ability in the shift from visual-cue learning to place response discrimination in rats. Conversely, SPS induced no effect on a place-to-cue set-shifting performance. Based on SPS-impaired set-shifting model, we used Western blot and immunofluorescent approaches to clarify SPS-induced alternations in synaptic plasticity and neuronal activation in the mPFC and NAc. Rats that were subjected to SPS exhibited a large increase in pSer845-GluA1 and total GluA1 levels in the mPFC, while no significant change in the NAc. We further found that exposure to SPS significantly decreased c-Fos expression in the NAc core but not the shell after set-shifting behavior. Whereas, enhanced c-Fos expression was observed in prelimbic and infralimbic cortices. Collectively, these findings suggest that abnormal hyperactivity in the mPFC and dysfunction in the NAc core underlie long-term deficits in executive function after traumatic experience, which might play an important role in the development of PTSD symptoms.
内侧前额叶皮质（mPFC）及其输出区域伏隔核（NAc）参与介导注意力的定势转换。创伤后应激障碍（PTSD）患者在将注意力从创伤性线索上脱离时存在困难，这与定势转换能力受损有关。然而，PTSD患者这种行为灵活性缺陷的基础是否是皮质纹状体功能改变尚不清楚。单次长时间应激（SPS）动物模型已被部分验证为PTSD模型，其中SPS大鼠重现了PTSD的病理生理异常和行为特征。在本研究中，我们首先发现暴露于SPS会损害大鼠从视觉线索学习转换到位置反应辨别的能力。相反，SPS对位置到线索的定势转换表现没有影响。基于SPS损伤的定势转换模型，我们使用蛋白质免疫印迹和免疫荧光方法来阐明SPS诱导的mPFC和NAc中突触可塑性和神经元激活的变化。遭受SPS的大鼠mPFC中pSer845-GluA1和总GluA1水平大幅增加，而NAc中无显著变化。我们进一步发现，在定势转换行为后，暴露于SPS会显著降低NAc核心而非壳核中的c-Fos表达。然而，在前边缘皮质和下边缘皮质中观察到c-Fos表达增强。总的来说，这些发现表明，mPFC异常亢进和NAc核心功能障碍是创伤经历后执行功能长期缺陷的基础，这可能在PTSD症状的发展中起重要作用。
