Sun Chung-Fu, Chang Chun-Hui
Institute of Systems Neuroscience, National Tsing Hua University, Hsinchu, Taiwan.
Brain Research Center, National Tsing Hua University, Hsinchu, Taiwan.
Front Behav Neurosci. 2022 Aug 22;16:981041. doi: 10.3389/fnbeh.2022.981041. eCollection 2022.
Obsessive-compulsive disorder (OCD) patients were usually found with the hyper-activation of the orbitofrontal cortex (OFC) and a deficit in fear extinction learning. The OFC can be subdivided into the lateral OFC (lOFC) and the medial OFC (mOFC). Previous studies have suggested that both subregions are involved in the modulation of negative emotions. However, how aberrant activation of the OFC interacts with the encoding of Pavlovian fear remains unknown. In this study, the lOFC or the mOFC was pharmacologically activated or inactivated before the fear conditioning on Day 1, followed by a context test on Day 2 and a tone test on Day 3 in male Long-Evans rats. We found that for the animals that underwent fear conditioning under aberrant activation of either the lOFC or the mOFC, they showed normal within-session fear expression. However, the acquisition/consolidation of contextual fear was impaired under mOFC activation, while the acquisition/consolidation of cued fear was impaired under either the lOFC or the mOFC activation, in that these animals showed lower freezing compared to controls during the retrieval test. On the other hand, for the animals that underwent fear conditioning under inactivation of either the lOFC or the mOFC, they showed normal within-session fear expression, as well as intact encoding of both the contextual and cued fear. Together, our results suggested that the OFC was not actively engaged in the acquisition of Pavlovian fear conditioning, but aberrant activation of the OFC impaired fear learning.
强迫症（OCD）患者通常表现为眶额皮质（OFC）过度激活以及恐惧消退学习缺陷。OFC可细分为外侧眶额皮质（lOFC）和内侧眶额皮质（mOFC）。先前的研究表明，这两个亚区域都参与负面情绪的调节。然而，OFC的异常激活如何与巴甫洛夫式恐惧的编码相互作用仍不清楚。在本研究中，在第1天进行恐惧条件反射之前，对雄性Long-Evans大鼠的lOFC或mOFC进行药理学激活或失活，随后在第2天进行情境测试，在第3天进行音调测试。我们发现，对于在lOFC或mOFC异常激活下接受恐惧条件反射的动物，它们在训练过程中的恐惧表达正常。然而，在mOFC激活下，情境恐惧的获得/巩固受损，而在lOFC或mOFC激活下，线索恐惧的获得/巩固受损，因为在检索测试中，这些动物的僵立程度低于对照组。另一方面，对于在lOFC或mOFC失活下接受恐惧条件反射的动物，它们在训练过程中的恐惧表达正常，并且情境恐惧和线索恐惧的编码均完整。总之，我们的结果表明，OFC并未积极参与巴甫洛夫式恐惧条件反射的获得，但OFC的异常激活会损害恐惧学习。
