The bed nucleus of the stria terminalis mediates inter-individual variations in anxiety and fear.
The bed nucleus of the stria terminalis mediates inter-individual variations in anxiety and fear.
复制标题
DOI：
10.1523/jneurosci.2119-09.2009
复制
发表时间：
2009-08-19
期刊：
影响因子：
--
通讯作者：
Paré D
中科院分区：
文献类型：
--
作者：
Duvarci S;Bauer EP;Paré D
虽然学习恐惧刺激来预测危险可以促进生存，但无法抑制对不适当线索的恐惧会导致回避行为的恶性循环。之前的研究已经揭示了恐惧反应的个体间的巨大差异，临床焦虑的人表现出一种将习得的恐惧概括为安全刺激或情况的倾向。为了阐明这些个体间差异的起源，我们让大鼠接受不同的听觉恐惧条件反射范式，其中一个条件听觉刺激(CS+)与足电击配对，而第二个条件听觉刺激(CS−)不配对。我们比较了训练前接受终纹床核兴奋性毒性损伤(BNST)的大鼠和假手术大鼠的行为。假手术大鼠表现出一系列的焦虑/恐惧行为。在连续体的一端，大鼠表现出区分CS+和CS−的能力较差，高度情景冻结，以及在高位加迷宫中表现出焦虑样特征。在另一端，大鼠对CS−表现出较少的恐惧，对环境的冻结程度较低，在EPM上表现出不焦虑的特征。尽管BNST损伤的大鼠对CS+获得了类似的高水平的条件性恐惧，但它们对CS−的冻结程度低于假手术大鼠。事实上，BNST损伤的大鼠表现得像具有高分辨能力的假大鼠，因为它们在EPM中表现出低背景恐惧和非焦虑的表型。总体而言，这表明恐惧泛化和焦虑表型的个体间差异是由BNST对杏仁核和/或其目标的影响决定的。
While learning to fear stimuli that predict danger promotes survival, the inability to inhibit fear to inappropriate cues leads to a pernicious cycle of avoidance behaviors. Previous studies have revealed large inter-individual variations in fear responding with clinically anxious humans exhibiting a tendency to generalize learned fear to safe stimuli or situations. To shed light on the origin of these inter-individual variations, we subjected rats to a differential auditory fear conditioning paradigm where one conditioned auditory stimulus (CS+) was paired to footshocks whereas a second (CS−) was not. We compared the behavior of rats that received pre-training excitotoxic lesions of the bed nucleus of the stria terminalis (BNST) to that of sham rats. Sham rats exhibit a continuum of anxious/fearful behaviors. At one end of the continuum were rats that displayed a poor ability to discriminate between the CS+ and CS−, high contextual freezing, and an anxiety-like trait in the elevated plus maze (EPM). At the other end were rats that display less fear generalization to the CS−, lower freezing to context, and a non-anxious trait on the EPM. Although BNST-lesioned rats acquired similarly high levels of conditioned fear to the CS+, they froze less than sham rats to the CS−. In fact, BNST-lesioned rats behaved like sham rats with high discriminative abilities in that they exhibited low contextual fear and a non-anxious phenotype in the EPM. Overall, this suggests that inter-individual variations in fear generalization and anxiety phenotype are determined by BNST influences on the amygdala and/or its targets.