Hippocampal cells segregate positive and negative engrams

The hippocampus contains neurons that correspond to two partially non-overlapping sets of positive and negative engrams, which may be distinguished by molecular, cellular, and projection-specific features. The hippocampus is involved in processing a variety of mnemonic computations specifically the spatiotemporal components and emotional dimensions of contextual memory. Recent studies have demonstrated cellular heterogeneity along the hippocampal axis. The ventral hippocampus has been shown to be important in the processing of emotion and valence. Here, we combine transgenic and all-virus based activity-dependent tagging strategies to visualize multiple valence-specific engrams in the vHPC and demonstrate two partially segregated cell populations and projections that respond to appetitive and aversive experiences. Next, using RNA sequencing and DNA methylation sequencing approaches, we find that vHPC appetitive and aversive engram cells display different transcriptional programs and DNA methylation landscapes compared to a neutral engram population. Additionally, optogenetic manipulation of tagged cell bodies in vHPC is not sufficient to drive appetitive or aversive behavior in real-time place preference, stimulation of tagged vHPC terminals projecting to the amygdala and nucleus accumbens (NAc), but not the prefrontal cortex (PFC), showed the capacity drive preference and avoidance. These terminals also were able to change their capacity to drive behavior. We conclude that the vHPC contains genetically, cellularly, and behaviorally segregated populations of cells processing appetitive and aversive memory engrams.

Automated summary

The hippocampus contains distinct populations of neurons responsible for processing positive and negative memories, which can be distinguished by their molecular, cellular, and projection-specific features. Recent studies have revealed cellular heterogeneity along the hippocampal axis, with the ventral hippocampus playing a significant role in emotion and valence processing. By combining different techniques, the researchers visualized valence-specific memory engrams in the ventral hippocampus, and found that these cells display different transcriptional programs and DNA methylation landscapes compared to neutral memory cells. Additionally, they demonstrated that stimulating the ventral hippocampus terminals projecting to certain brain regions can drive preference and avoidance behaviors. This study highlights the importance of the ventral hippocampus in processing appetitive and aversive memories.