Ventral hippocampal regulation of contextual fear and extinction memory

Fear learning creates long-term memories through which predictive cues or the context surrounding the fearful event acquire negative associations. Later exposure to these stimuli elicits a fearful response, but this learned response will diminish in the absence of threat, a process known as extinction. Extinction does not abolish fear memory, but instead creates a separate memory of safety. The hippocampus is thought to be a hub for competition of the expression of these two opposing memories. Neural ensemble representations of contextual fear and extinction memories are distinct in the hippocampus, but how these memories are processed to influence recall and behavior is not known. These experiments sought to investigate activity in the ventral CA1 and subiculum (vHP), where projections to other fear and extinction related structures are located, to better understand how the hippocampus influences the expression and suppression of fear behavior. First, we investigated whether activity among vHP projections to the BLA and IL differed during context fear and extinction recall. We found that fear recall causes more activation of projections to BLA compared to IL, while extinction recall results in the opposite pattern of more activation of projections to IL than BLA. This shows that the ventral hippocampus is sensitive to the valence of contextual memory, and signals to relevant brain regions based on that valence. Next, we sought to selectively inhibit the projections from vHP to BLA and IL to test if these projections are indeed necessary for further recall of these memories. These manipulations were unsuccessful in impairing recall. Finally, we stimulated SST interneurons in vHP or IL to induce feed-forward inhibition. We found that stimulating vHP SST interneurons impaired fear recall, reducing fear behavior, and impaired extinction learning, resulting in higher fear behavior in a later test. This result demonstrates the vHP’s role in both context fear expression and suppression. Increasing inhibition in the IL did not affect context fear or extinction recall but did impair auditory cue extinction. Overall, these results provide evidence that vHP activity modulates context memory in a valence dependent way through connections to other fear related regions.