To interrogate whether altered function of the hippocampal-mPFC circuit underlies the deficit in fear extinction recall in rats subjected to single-prolonged stress (SPS), changes in brain region-specific metabolic rate were measured in male rats (control and SPS treated). Brain region metabolic rates were quantified using uptake of ¹⁴C-2-deoxyglucose (¹⁴C-2DG) during fear memory formation, fear memory extinction and extinction recall. Control and SPS rats had similar regional brain activities at baseline. During extinction recall, ¹⁴C-2DG uptake decreased in hippocampal regions in control rats, but not in SPS rats. SPS rats also exhibited a significant deficiency in fear extinction recall, replicating a previously reported finding. Reduced hippocampal activity during fear extinction recall in control animals may reflect reduction in fear overgeneralization, thereby enabling discrimination between distinct contexts. In contrast, persistent levels of hippocampal activity in SPS-exposed male animals during fear extinction recall may reflect the dysfunctional persistence of fear overgeneralization. Future studies in females can test gender-specificity of these effects, with appropriate attention to luteal dependent effects on extinction of fear learning. Detailed knowledge of regional brain activities underlying stress-induced deficits in extinction recall may help identify therapeutic targets in PTSD.

为了探究海马-mPFC 回路的功能改变是否是遭受单次长期应激 (SPS) 的大鼠的恐惧消退回忆缺陷的基础，测量了雄性大鼠（对照组和 SPS 治疗）大脑区域特异性代谢率的变化。在恐惧记忆形成、恐惧记忆消退和消退回忆期间，使用¹⁴ C-2-脱氧葡萄糖 ( ¹⁴ C-2DG) 的摄取来量化大脑区域代谢率。对照组和 SPS 大鼠在基线时具有相似的区域脑活动。在灭绝召回期间，¹⁴对照大鼠海马区的 C-2DG 摄取减少，但 SPS 大鼠没有。SPS 大鼠还表现出恐惧消退回忆的显着缺陷，重复了先前报告的发现。对照动物在恐惧消退回忆期间海马活动的减少可能反映了恐惧过度泛化的减少，从而能够区分不同的背景。相比之下，在恐惧灭绝回忆期间，暴露于 SPS 的雄性动物海马活动的持续水平可能反映了恐惧过度泛化的功能失调持续存在。未来对女性的研究可以测试这些影响的性别特异性，并适当关注黄体依赖性对恐惧学习消退的影响。