Altered hippocampal function before emotional trauma in rats susceptible to PTSD-like behaviors.
Altered hippocampal function before emotional trauma in rats susceptible to PTSD-like behaviors.
复制标题
在易受 PTSD 样行为影响的大鼠中，在情绪创伤之前改变海马功能。
DOI：
10.1016/j.nlm.2014.02.006
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发表时间：
2014
影响因子：
2.7
通讯作者：
Vazdarjanova,Almira
中科院分区：
文献类型：
--
作者：
Nalloor,Rebecca;Bunting,KristopherM;Vazdarjanova,Almira
创伤后应激障碍（PTSD）是一种在经历创伤事件后发生的焦虑症。PTSD的易感性是存在的，因为只有一些创伤暴露的个体会发展这种情况。在动物模型中研究易感性有助于理解疾病的病因。我们先前报道了一种动物模型，该模型允许将大鼠可靠地预先分类为在后来的创伤后发展PTSD样表型的易感性（Sus）或抗性（Res）。在这里，我们报告说，Sus，与Res相比，大鼠在经历创伤事件之前，海马功能发生了改变，沿着隔颞轴。在实验I中，Res和Sus大鼠探索了一个新的盒子两次。使用细胞成像方法评估可塑性相关的立即早期基因表达的大型神经元合奏，弧/Homer 1acatFISH，我们发现，SUS大鼠有较小的vCA 3合奏在第二次勘探。Sus大鼠中vCA 3激活的抑制并不是由于探索行为的差异，也不是由于基底外侧杏仁核（BLA）中Arc/Homer 1a表达的差异。BLA是vCA 3输入的主要来源，但在两次探索期间激活的BLA集合的集合大小和重叠与Res大鼠相似。此外，Sus大鼠在第二次事件的背侧海马表达中有显著的“不忠”：与Res大鼠相比，在两次探索期间激活的Arc/Homer 1a表达集合的重叠较低（集合的大小与Res大鼠相似）。这些差异只在压力相对较低的条件下才被发现，因为当Sus和Res大鼠经历恐惧条件反射时，它们没有被观察到（实验II）。综合起来，研究结果表明，在易感大鼠经历情感创伤之前，海马功能存在改变，并表明这是PTSD的一个危险因素。
Posttraumatic stress disorder (PTSD) is an anxiety disorder that occurs after experiencing a traumatic event. Susceptibility to PTSD exists, as only some trauma-exposed individuals develop this condition. Investigating susceptibilities in animal models can contribute to understanding the etiology of the disorder. We previously reported an animal model which allows reliable pre-classification of rats as susceptible (Sus) or resistant (Res) to developing a PTSD-like phenotype after a later trauma. Here we report that Sus, compared to Res, rats have altered hippocampal function, along the septo-temporal axis, prior to experiencing a traumatic event. In Experiment I, Res and Sus rats explored a novel box twice. Using a cellular imaging method for assessing plasticity-related immediate-early gene expression in large neuronal ensembles,Arc/Homer1acatFISH, we show that Sus rats have smaller vCA3 ensembles during the second exploration. This suppressed vCA3 activation in Sus rats was not due to a difference in exploratory behavior, or to a difference inArc/Homer1aexpression in the basolateral amygdala (BLA). BLA is a main source of inputs to vCA3, but both the ensemble size and overlap of BLA ensembles activated during the two explorations was similar to that of Res rats. Additionally, Sus rats had significant ’infidelity’ in their dorsal hippocampal representations of the second event: a lower overlap, compared to Res rats, ofArc/Homer1a-expressing ensembles activated during the two explorations (the size of the ensembles were similar to those of Res rats). These differences were revealed only in conditions of relatively low stress, because they were not observed when Sus and Res rats experienced fear conditioning (Experiment II). Combined, the findings show that altered hippocampal function exists before experiencing emotional trauma in susceptible rats and suggest that this is a risk factor for PTSD.