Stress-induced alterations in prefrontal cortical dendritic morphology predict selective impairments in perceptual attentional set-shifting
Stress-induced alterations in prefrontal cortical dendritic morphology predict selective impairments in perceptual attentional set-shifting
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DOI：
10.1523/jneurosci.1184-06.2006
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发表时间：
2006-07-26
影响因子：
5.3
通讯作者：
McEwen, Bruce S.
中科院分区：
文献类型：
--
作者：
Liston, Conor;Miller, Melinda M.;McEwen, Bruce S.
压力生活事件在临床上与精神疾病的发病机制有关，但可能解释这一观察结果的神经基质仍然知之甚少。这些精神疾病的症状性注意缺陷与前额皮质结构网络的结构和功能异常有关。在这里，我们研究了慢性应激诱导的内侧前额叶皮层（mPFC）和眶额叶皮层（OFC）的树突改变是否为它们所服务的行为受损的基础。在21 d的重复约束应激后，对大鼠进行知觉注意设置转移任务测试，该任务产生了可分离的逆转学习和注意设置转移的测量，这两个功能分别由OFC和mPFC介导。在这些大鼠的一个亚群中进行路西法黄细胞内离子电泳注射，以检测mPFC和外侧OFC的第II/III层锥体细胞的树突形态。慢性应激诱导了注意力转移的选择性损伤和相应的mPFC顶端树突乔木的收缩（20%）。在应激大鼠中，而不是在对照组中，mPFC中树突状树突的减少预示着注意力转移能力的受损。相反，没有发现压力对翻转学习或外侧OFC的树突形态有不利影响。相反，OFC的顶端树枝状乔木增加了43%。这项研究提供了第一个直接证据，证明前额叶皮层的树突重塑可能是注意力控制功能缺陷的基础，而注意力控制功能缺陷是与压力相关的精神疾病的症状。
Stressful life events have been implicated clinically in the pathogenesis of mental illness, but the neural substrates that may account for this observation remain poorly understood. Attentional impairments symptomatic of these psychiatric conditions are associated with structural and functional abnormalities in a network of prefrontal cortical structures. Here, we examine whether chronic stress-induced dendritic alterations in the medial prefrontal cortex (mPFC) and orbital frontal cortex (OFC) underlie impairments in the behaviors that they subserve. After 21 d of repeated restraint stress, rats were tested on a perceptual attentional set-shifting task, which yields dissociable measures of reversal learning and attentional set-shifting, functions that are mediated by the OFC and mPFC, respectively. Intracellular iontophoretic injections of Lucifer yellow were performed in a subset of these rats to examine dendritic morphology in layer II/III pyramidal cells of the mPFC and lateral OFC. Chronic stress induced a selective impairment in attentional set-shifting and a corresponding retraction (20%) of apical dendritic arbors in the mPFC. In stressed rats, but not in controls, decreased dendritic arborization in the mPFC predicted impaired attentional set-shifting performance. In contrast, stress was not found to adversely affect reversal learning or dendritic morphology in the lateral OFC. Instead, apical dendritic arborization in the OFC was increased by 43%. This study provides the first direct evidence that dendritic remodeling in the prefrontal cortex may underlie the functional deficits in attentional control that are symptomatic of stress-related mental illnesses.