PSYCH OpenIR  > 健康与遗传心理学研究室
Alternative TitleRole of prelimbic cortex – nucleus accumbens circuit in attentional set-shifting
Abstract认知灵活性(Cognitive flexibility) 是指个体在环境事件发生改变的情况下,转变反应策略和应对模式的能力。 多种精神疾患的病人会有认知灵活性受损的表现,如创伤后应激障碍,精神分裂症和抑郁症等,而应激往往是这些精神障碍的一个重要影响因素。应激可能导致调控认知灵活性功能的重要脑区——前额叶皮层(Prefrontal cortex)发生结构和功能的变化,从而导致认知灵活性功能的变化。
1.为探索创伤性应激对认知灵活性的影响,本实验使用了单一连续应激(Single prolonged stress,  SPS)处理动物,结果发现 SPS 处理对认知灵活性的两个功能模块有不同影响,暴露于SPS 的动物定势转移能力下降,而反转学习任务表现提升。这两种功能的不同变化可能都与内侧前额叶皮层(Medial prefrontal cortex,mPFC)的功能变化有关。因此,我们通过检测 c-Fos 蛋白表达量和谷氨酸AMPA 受体GluA1亚基磷酸化水平,分析了经 SPS 处理的动物在完成定势转移任务时 mPFC 和其重要输出脑区伏隔核(Nucleus accumbens,NAc)的神经元激活水平和突触可塑性变化。结果发现,与控制组动物相比,暴露于SPS 处理的动物在进行定势转移任务时边缘前皮层(Prelimbic cortex,PL)和边缘下皮层(Infralimbic cortex,IL)脑区激活显著增高,NAc核心部激活水平下降,且PL脑区GluA1 表达总量和其丝氨酸 845位点的磷酸化水平上升。以上结果提示, SPS 处理导致的定势转移能力下降可能和应激后 PL和NAc 核心部脑区的功能变化和突触可塑性变化有关。
2.  为进一步明确 PL−NAc神经环路是否参与调控定势转移能力,我们首先通过两种正向和逆向两种示踪方法确认了 PL和NAc核心部的神经投射,并检测了动物进行定势转移任务时PL和NAc核心部以及与其相关联的其他9个脑区的激活状态。结果显示,在记忆提取至策略转换的过程中,PL,NAc 核心部和无颗粒岛叶皮质(Agranular insular cortex,AI)激活水平表现为同步地先升高再下降,而杏仁核外侧基底前部 (Anterior part of basolateral amygdaloid nucleus,   BLA)的激活水平则在定势转移任务时进一步增高。这种脑区激活水平动态的变化过程,可能反映了可能代表了动物打破旧策略——形成新策略——稳定执行新策略这一过程。最后,我们尝试应用光遗传学的方法,激活 PL脑区,模拟该脑区规则尖峰神经元的放电模式,结果发现这种处理显著提升了动物在定势转移能力中的表现,并降低了固着错误(Perseverative errors,PE),该结果提示PL脑区的规则尖峰神经元在定势转移任务中建立新规则这一阶段起着重要作用。
以上结果表明,PL-NAc 核心部通路协同其他脑区动态调控策略转换过程,在定势转移功能中起重要作用。
Other AbstractCognitive flexibility  is the ability to update behavior and modify strategy in response to changing situational demands.  To be adaptive and flexible is not only essential for daily function, but also behavioral flexibility impairments are found in psychiatric disorders such as post-traumatic stress disorder (PTSD), schizophrenia and depression. Stress appears to be an important factor contributing to  these psychiatric disorders.    Stress  can affect functions  and  synaptic  plasticity  in  medial prefrontal cortex  (mPFC), which is a critical brain area  required for  cognitive flexibility. The aim of present study was to investigate whether exposure to traumatic stress would affect performance of set-shifting and reversal learning task, and the role of prefrontal cortex – nucleus accumbens circuit in mediating cognitive flexibility.  
Two parts of experiments were performed as followed:
1.  To assess whether exposure to traumatic stress would impair performance on the set-shifting and reversal learning task,  rats were subjected to  single prolonged stress (SPS). SPS induced set-shifting deficit, but facilitated reversal learning. The set-shifting impairment was associated with increased neuronal activation in prelimbic cortex  (PL) and infralimbic cortex  (IL), and decreased  activation in Nucleus accumbens  (NAc) core. Also, rats received stress had a  significant increase in  total GluA1 expression level and phosphorylation level of GluA1  at Serine-845  site in PL.  These findings  indicate  that  SPS-induced  set-shifting deficits might  result  from  alternation of functions and  synaptic plasticity  in  PL and NAc core.
2.  To elucidate whether  PL-NAc  circuit specifically participates in attentional set-shifting task, we confirmed the efferent of PL and projection to NAc core, and then assessed the neuronal activation of  these  areas after set-shifting task  by evaluation the c-Fos expression.  Synchronously  dynamic  changes in activation level were found in PL,NAc core, agranular insular cortex, and the anterior part of  basolateral amygdaloid nucleus.  These results indicate that the dynamic changes in activation of PL may be involved in the shifting from implementation of a well-established rule to  learning a new  strategy.  Finally, we demonstrated that activation of regular spiking neuron in PL by optogenetic approach facilitated set-shifting performance. These may indicate the role of regular spiking neuron in PL in learning new strategy.
Using several approaches, this study provides convergent support  for a dynamic role of PL-NAc circuit in mediating set-shifting.  
Subject Area医学心理学
Keyword定势转移 边缘前皮层 伏隔核核心区 规则尖峰神经元 单一连续应激
Degree Discipline心理学
Degree Grantor中国科学院研究生院
Place of Conferral北京
Document Type学位论文
Recommended Citation
GB/T 7714
朴成姬. 边缘前皮层-伏隔核神经通路在定势转移任务中的作用研究[D]. 北京. 中国科学院研究生院,2015.
Files in This Item:
File Name/Size DocType Version Access License
朴成姬-硕士学位论文.pdf(4087KB)学位论文 限制开放CC BY-NC-SAApplication Full Text
Related Services
Recommend this item
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[朴成姬]'s Articles
Baidu academic
Similar articles in Baidu academic
[朴成姬]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[朴成姬]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.