Phosphorylated cyclic AMP response element binding protein expression induced in the periaqueductal gray by predator stress: its relationship to the stress experience, behavior and limbic neural plasticity
Phosphorylated cyclic AMP response element binding protein expression induced in the periaqueductal gray by predator stress: its relationship to the stress experience, behavior and limbic neural plasticity
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DOI：
10.1016/j.pnpbp.2003.09.017
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发表时间：
2003-12-01
影响因子：
5.6
通讯作者：
Burton, P
中科院分区：
文献类型：
--
作者：
Adamec, RE;Blundell, J;Burton, P
在猫和最近在大鼠的电生理学研究牵连在中脑导水管周围灰质（PAG）的神经可塑性及其传入压力引起的恐惧行为和焦虑样行为（ALB）的增加。这种增加可能模拟人类创伤应激后情感变化的各个方面。本研究探讨了PAG的神经可塑性及其与杏仁中央核（ACE）在雄性啮齿动物捕食应激焦虑样反应中的作用。在两项研究的第一项中，研究了捕食者应激对磷酸化环磷酸腺苷反应元件结合蛋白（pCREB）诱导的影响。免疫组化检测PAG和下丘脑腹内侧区（VMH）pCREB表达。捕食者应激增加了PAG细胞中pCREB的表达程度（光密度测量），但没有增加表达pCREB的细胞数量（体视学测量）。此外，pCREB样免疫反应性（lir）的捕食者应激特异性增加仅限于PAG的右侧柱。此外，右侧列中的pCREB lir可能反映了应激经历的方面，因为应激源（猫行为）和对应激源的反应（大鼠防御行为）高度预测pCREB表达的程度。由于pCREB表达与神经传递的持久增强（LLP）有关，因此在第二项研究中，我们研究了捕食者应激对ACE-PAG通路传递的影响。捕食者应激后11 - 12天，右半球ACE-PAG传输的诱发电位测量值升高，但左半球没有。这一发现与药物应激对猫右半球杏仁核-PAG传递的长期影响一致，但在猫左半球则不然。令人感兴趣的是，应激源经历和对应激源的反应的相同方面（其预测pCREB表达的程度）也高度预测ACE-PAG传递的测量的增强程度。行为分析表明，最一致的影响，捕食者的压力是在加迷宫（开放臂探索和风险评估）和惊吓的行为。此外，协方差分析表明，ACE-PAG增强介导的一些，但不是所有的变化，在ALB产生的捕食压力。由于pCREB表达可能是某些形式的记忆和LLP中神经可塑性变化的前体，因此本研究结果补充了猫的研究，表明PAG中的神经可塑性变化是压力后影响变化的基础。此外，这些研究结果表明，PAG中的神经可塑性变化可能是捕食者应激诱导的啮齿动物情感行为变化的重要介质。最后，与猫和人类的研究一致，右半球在对压力的长期反应中显得特别重要。(C)2003年由Elsevier Inc.出版
Electrophysiological studies in cats and recently in rats implicate neuroplasticity in the periaqueductal gray (PAG) and its afferents in stressor-induced increases in fearful behavior and anxiety-like behavior (ALB). Such increases may model aspects of affective changes following traumatic stress in humans. The present study explored the role of neuroplasticity in PAG and its connection with the central nucleus of the amygdala (ACE) in male rodent anxiety-like response to predator stress. In the first of two studies, the effects of predator stress on the induction of phosphorylated cyclic AMP response element binding protein (pCREB) were investigated. pCREB expression in the PAG and ventromedial hypothalamus (VMH) was examined immunohistochemically. Predator stress increased the degree of pCREB expression in PAG cells (measured densitometrically) but did not increase the number of cells expressing pCREB (measured stereologically). Moreover, predator stress-specific increase in pCREB-like immunoreactivity (lir) was restricted to the right lateral column of the PAG. In addition, pCREB lir in the right lateral column likely reflects aspects of the stress experience because the stressor (cat behavior) and the response to the stressor (rat defensive behavior) are highly predictive of degree of pCREB expression. There was no effect of predator stress on pCREB lir in the VMH.Because pCREB expression has been associated with long-lasting potentiation (LLP) of neural transmission, we examined the effects of predator stress on transmission in the ACE-PAG pathway in a second study. Predator stress elevated evoked potential measures of ACE-PAG transmission in the right hemisphere but not in the left hemisphere 11 - 12 days after predator stress. This finding is consistent with the longer-lived effects of pharmacological stress on amygdalo-PAG transmission in the right hemisphere but not in the left hemisphere in cats. Of interest is the fact that the same aspects of the stressor experience and reaction to it, which are predictive of the degree of pCREB expression, are also highly predictive of the degree of potentiation of measures of ACE-PAG transmission. Behavioral analyses revealed that the most consistent effects of predator stress are on behavior in the plus maze (open arm exploration and risk assessment) and on startle. In addition, covariance analysis suggests that ACE-PAG potentiation mediates some but not all of the changes in ALB produced by predator stress. Because pCREB expression may be a precursor to neuroplastic changes in certain forms of memory and LLP, the present findings complement studies in the cat, showing that neuroplastic changes in the PAG underlie changes in affect following stress. Furthermore, these findings suggest that neuroplastic changes in PAG may be important mediators of predator stress-induced changes in affective behavior in rodents. Finally, consistent with cat and human studies, the right hemisphere appears particularly important in long-term response to stress. (C) 2003 Published by Elsevier Inc.