Hippocampal cells multiplex positive and negative engrams

ABSTRACT: The hippocampus is involved in processing a variety of mnemonic computations including the spatiotemporal components, as well as the corresponding emotional dimensions, of contextual memory.1-3 Recent studies have demonstrated vast structural and functional heterogeneity along the dorsal-ventral axis1,5 of the hippocampus, and while much is known about how the dorsal hippocampus processes spatial-temporal content, much less is known about whether or not the ventral hippocampus (vHPC) partitions positive and negative experiences into distinct sets of cells.4-9 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 positive and negative experiences. Next, using an RNA sequencing approach, we find that vHPC positive and negative engram cells display distinct transcriptional programs compared to a neutral engram population. Additionally, while optogenetic manipulation of tagged cell bodies in vHPC is not sufficient to drive preference or avoidance, stimulation of tagged vHPC terminals projecting to the amygdala and nucleus accumbens (NAc), but not the prefrontal cortex (PFC), drives preference and avoidance. These terminals also can undergo a “switch” or “reset” in their capacity to drive either, thereby demonstrating their flexible contributions to behavior. We conclude that the vHPC contains genetically, cellularly, and behaviorally distinct populations of cells processing positive and negative memory engrams. Together, our findings provide a novel means by which to visualize multiple engrams within the same brain and point to their unique genetic signatures as reference maps for the future development of new therapeutic strategies.

ORGANISM(S): Mus musculus

PROVIDER: GSE198731 | GEO | 2022/07/13

REPOSITORIES: GEO