Population and Projection-Specific Segregation of Fear and Reward in the Hippocampus

Abstract

The ventral hippocampus (vHPC) has the capacity to encode spatial and emotional information. Here, we utilize activity-dependent tagging strategies and provide evidence that the vCA1 recruits two segregated populations of cells in response to either rewarding or aversive stimuli. While optogenetic manipulation of tagged cell bodies in vHPC is not sufficient to drive behavior, vHPC terminals projecting to the amygdala and nucleus accumbens, but not the prefrontal cortex, have both the ability to drive preference and aversion, as well as to “switch” their capacity to drive either. Next, we develop a novel “dual memory tagging” approach and drive aversive and reward-like behaviors by utilizing blue- and red-shifted rhodopsins in a within-subject manner. Finally, using an RNA Sequencing approach, we find that vHPC fear and reward cells are genetically distinct cellular populations and upregulate genes associated with Alzheimer’s Disease and neuroprotection, respectively. We conclude that the vHPC recruits genetically, anatomically, and behaviorally distinct cellular populations processing fear and reward.