Glutamatergic neurons in the dorsal hippocampus modulate odor-associated fear generalization

Over-generalization of fear is a common feature of anxiety disorders. Numerous studies have demonstrated the role of the bilateral dorsal hippocampus in regulating memory formation and retrieval; however, the role of the dorsal hippocampus in regulating cue-associated fear memory generalization remains unclear. Here, we systematically investigated the roles of the dorsal hippocampus in odor-associated fear generalization. Our data showed that high-intensity fear training activated both glutamatergic neurons in the dorsal CA1 (dCA1) and dorsal dentate gyrus (dDG). Through chemogenetic suppression of diverse regions in the dorsal hippocampus, we observed that glutamatergic neurons in the dorsal CA1 alleviated odor-associated fear generalization. Together, our findings reveal mechanisms of the dorsal hippocampus in regulating cue-induced fear generalization and may offer new insights into the role of the hippocampus in the pathogenesis of memory-related and anxiety disorders.