VIP+ interneuron control of the hippocampal cognitive map.

The hippocampus is known for spatial mapping through place cells, but much less is understood about the cognitive map that integrates task and reward information. Recent work has identified elements of this map as "reward" cells that encode distance relative to rewards. However, their detailed characteristics, regulatory mechanisms, and importance for goal-oriented behavior remain unknown. Using a virtual reality task with multiple shifts of a hidden reward zone and two-photon calcium imaging in mice, we characterized the coding properties of pyramidal neurons, identifying place cells and reward cells that were active at consistent distances from rewards. The lifetime of both reward and place cells was short, lasting a few reward translocations, but reward cells persisted longer than place cells within and across days. Reward and place cell populations remained largely segregated across reward shifts, suggesting reward-cell-specific regulation mechanisms. Indeed, we identified vasoactive intestinal peptide (VIP+) interneuron activity as a critical regulator of reward cell formation and task performance. Optogenetic inhibition of VIP+ neurons reduced reward cell numbers, decreased goal representation, and impaired task performance. Activation produced the opposite with increased reward cells, stronger goal representation, and enhanced performance. Surprisingly, this circuit regulation was largely specific to reward cells since the spatial map was unchanged by VIP+ activity manipulation, with no alteration in place cell number or position decoding. Our findings reveal that reward cell activity is necessary for flexible, goal-directed learning, and VIP+ neuronal activity plays a specific role in controlling the formation and coding of this cognitive map.