Inactivation of medial or lateral orbitofrontal cortex during fear extinction did not interfere with fear renewal

• Published in: Neurobiology of learning and memory Vol. 204; p. 107800
• Main Authors: Shih, Cheng-Wei, Chang, Chun-hui
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-10-2023
• Subjects: exposure therapy; fear renewal; obsessive-compulsive disorder; orbitofrontal cortex; rats; orbitofrontal cortex; fear renewal; exposure therapy; rats; obsessive-compulsive disorder
• ISSN: 1074-7427; 1095-9564
• DOI: 10.1016/j.nlm.2023.107800

•Inactivation of lateral OFC interfered with within-session fear expression.•OFC inactivation during extinction left context-dependent fear retrieval intact.•OFC is not actively engaged in fear regulation under normal circumstances.
Hyperactive orbitofrontal cortical activation is commonly seen in patients of obsessive-compulsive disorder (OCD). Previous studies from our laboratory showed that for rats with aberrant activation of the orbitofrontal cortex (OFC) during the extinction phase, they were unable to use contexts as the reference for proper retrieval of fear memory during renewal test. This result supported the phenomenon that many OCD patients show poor regulation of fear-related behavior. Since there are robust anatomical connections of the OFC with the fear-circuit, we aim to further examine whether the OFC is actively engaged in fear regulation under normal circumstances. In this study, the lateral or medial OFC was inactivated during the extinction phase using the ABA fear renewal procedure. We found that these animals showed intact fear renewal during retrieval test with their freezing levels equivalent to the control rats, revealing that the OFC did not have decisive roles in extinction acquisition. Together with our previous study, we suggest that the OFC only interferes with fear regulation when it becomes pathophysiologically hyperactive.