Dissociated roles of dorsal and ventral hippocampus in recall and extinction of conditioned fear in male and female juvenile rats

• Published in: Experimental neurology Vol. 329; p. 113306
• Main Authors: Park, Chun Hui J., Ganella, Despina E., Perry, Christina J., Kim, Jee Hyun
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2020
• Subjects: Animals; Conditioning, Classical - drug effects; Conditioning, Classical - physiology; Development; Extinction; Extinction, Psychological - drug effects; Extinction, Psychological - physiology; Fear; Fear - drug effects; Fear - physiology; Fear - psychology; Female; Freezing; GABA-A Receptor Agonists - administration & dosage; Hippocampus; Hippocampus - drug effects; Hippocampus - physiology; Infusions, Intraventricular; Juvenile; Male; Mental Recall - drug effects; Mental Recall - physiology; Muscimol - administration & dosage; Rat; Rats; Rats, Sprague-Dawley; Renewal; Sex differences; Juvenile; Fear; Rat; Extinction; Development; Sex differences; Female; Renewal; Hippocampus; Freezing
• ISSN: 0014-4886; 1090-2430; 1090-2430
• DOI: 10.1016/j.expneurol.2020.113306

Reduction of conditioned fear expression by extinction underlies cue exposure therapies that treat anxiety disorders. Extinction is context-specific. Renewal, for example, is the relapse of extinguished fear when subjects are tested in a different context to extinction. This context-specificity is developmentally regulated and sex-dependent, with renewal being observed in postnatal day (P) 18 female, but not in male, rats. Given the hippocampus (HPC) is critical for context-specific extinction in adult rodents, we investigated dorsal or ventral hippocampus (dHPC or vHPC) involvement in context-specific extinction in P18 male and female rats. We microinfused muscimol (GABAA agonist) to inactivate either structure before extinction, then tested rats for renewal the next day. Regardless of sex, dHPC inactivation accelerated extinction acquisition, while vHPC inactivation reduced fear expression during extinction and impaired extinction recall. Consistent with previous findings, renewal was observed in females but not in males. Surprisingly, inactivation of dHPC or vHPC had no effects on renewal in either sex, indicating that the hippocampus does not play a critical role in context-dependent extinction learning in juvenile rats. These findings are the first to demonstrate dissociated roles of dHPC and vHPC in conditioned fear expression and extinction in juvenile rats. In addition, context-specific extinction shown by juvenile females, but not males, likely is not due to potential sex differences in hippocampus involvement in extinction of conditioned fear in developing rats. •Inactivation of dorsal hippocampus accelerated extinction in juvenile rats.•Inactivation of ventral hippocampus impaired extinction recall in juvenile rats.•Renewal of extinguished fear was observed in juvenile females but not males.•Hippocampus inactivation did not affect sex differences in renewal.