National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, 560065, India.
Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, EH8 9XD, UK.
Neuropsychopharmacology. 2022 May;47(6):1145-1155. doi: 10.1038/s41386-021-01230-z. Epub 2021 Nov 30.
Disruptions in amygdalar function, a brain area involved in encoding emotionally salient information, has been implicated in stress-related affective disorders. Earlier animal studies on the behavioral consequences of stress-induced abnormalities in the amygdala focused on learned behaviors using fear conditioning paradigms. If and how stress affects unconditioned, innate fear responses to ethologically natural aversive stimuli remains unexplored. Hence, we subjected rats to aversive ultrasonic vocalization calls emitted on one end of a linear track. Unstressed control rats exhibited a robust avoidance response by spending more time away from the source of the playback calls. Unexpectedly, prior exposure to chronic immobilization stress prevented this avoidance reaction, rather than enhancing it. Further, this stress-induced impairment extended to other innately aversive stimuli, such as white noise and electric shock in an inhibitory avoidance task. However, conditioned fear responses were enhanced by the same stress. Inactivation of the basolateral amygdala (BLA) in control rats prevented this avoidance reaction evoked by the playback. Consistent with this, analysis of the immediate early gene cFos revealed higher activity in the BLA of control, but not stressed rats, after exposure to the playback. Further, in vivo recordings in freely behaving control rats exposed to playback showed enhanced theta activity in the BLA, which also was absent in stressed rats. These findings offer a new framework for studying stress-induced alterations in amygdala-dependent maladaptive responses to more naturally threatening and emotionally relevant social stimuli. The divergent impact of stress on defensive responses--impaired avoidance responses together with increased conditioned fear--also has important implications for models of learned helplessness and depression.
杏仁核功能障碍,即参与编码情绪相关信息的大脑区域,与应激相关的情感障碍有关。早期关于应激引起的杏仁核异常对行为后果的动物研究,主要集中在使用恐惧条件反射范式的习得行为上。应激是否以及如何影响对生态自然厌恶刺激的非条件、先天的恐惧反应,仍未得到探索。因此,我们让大鼠接触在线性轨道一端发出的厌恶超声发声。未受应激的对照大鼠通过远离回放声音源,表现出强烈的回避反应。出乎意料的是,先前暴露于慢性束缚应激会阻止这种回避反应,而不是增强它。此外,这种应激引起的损伤还扩展到其他先天厌恶刺激,如抑制性回避任务中的白噪声和电击。然而,相同的应激增强了条件性恐惧反应。在对照大鼠中,杏仁核基底外侧核(BLA)的失活阻止了由回放引发的这种回避反应。这与 cFos 即时早期基因的分析结果一致,即在接触回放后,BLA 中控制而非应激大鼠的活性更高。此外,在暴露于回放的自由行为对照大鼠的体内记录显示 BLA 中的θ活动增强,而应激大鼠中则没有。这些发现为研究应激引起的杏仁核依赖性适应不良反应对更自然威胁和情绪相关社会刺激的改变提供了一个新的框架。应激对防御反应的不同影响——回避反应受损,同时条件性恐惧增加——对习得性无助和抑郁的模型也有重要意义。