Genetically distinct parallel projection populations from ventral hippocampus to prefrontal cortex

The ventral hippocampus is proposed to perform its multitude of roles via segregated populations of neurons identified by either genetic makeup, downstream projection, or their combination. Recently we described two parallel projections from ventral hippocampus to prefrontal cortex, segregated across the radial axis of the CA1 and subicular areas. These two populations had distinct afferent and efferent connectivity and distinct influence of approach avoidance behaviour. In this study, we extend these data by performing RNA sequencing of each population of neurons. We find that these two populations have multiple genes that are differentially expressed. These genes correspond both to genes classically thought to be distributed across the radial axis such as Calbindin 1 and Pcp4, but also to more unexpected genes including postsynaptic scaffolds and GABA receptor subunits. Notably, a number of genes differentially expressed across the two populations were associated with the development of mental illness, suggesting an imbalance in the function of these two pathways in disease may be an interesting area for future research. Together, these data reinforce the dissociation of function of projections to prefrontal cortex across the radial axis of the ventral hippocampus, and provide multiple targets for both the genetic and functional dissociation of these roles.