Ventral Hippocampus Modulates Prefrontal Control of Background Contextual Fear After Cued Extinction

Understanding the neural mechanisms underlying fear extinction is crucial for improving anxiety disorder treatments. Previous studies have shown that activity in the ventral hippocampus (vHPC) to prelimbic cortex (PL) pathway regulates conditioned fear towards discrete cues after extinction. However, its role in contextual fear was unclear. In this study, we used optogenetics in rats to selectively stimulate vHPC terminals in the PL, which in anaesthetized animals led to responses in approximately 12% of PL neurons. In freely behaving animals, stimulating vHPC-PL projections during baseline context exposure, prior to the presentation of any discrete cue in post-extinction fear renewal tests, decreased contextual fear without affecting motricity or contextual fear immediately after conditioning. These results indicate that vHPC-PL projections modulate contextual fear expression after extinction. While task-specific features may contribute to the observed effect, our study fills a gap in understanding how the interaction between the vHPC and the mPFC regulates fear expression when contextual recall is followed by an extinction session.