The Dorsal CA2 to Ventral CA1 Circuit Contributes to Spatial and Context-Dependent Memories.

The hippocampal dorsal CA2 subregion (dCA2) is critical for social memory; however, its contribution to other types of hippocampus-dependent memories is not well understood. Here, we performed dCA2-specific circuit tracing, single-neuron projectome analysis, photometric Ca2+ imaging, and optogenetic manipulations to study the physiological roles of dCA2 neurons and their axon projections in behavioral paradigms for novel object recognition, novel location recognition, and contextual fear memory. We found that dCA2 neurons sent their strongest axon projections to the dorsal portion of ventral CA1 (vCA1d) and showed object and location-specific Ca2+ responses. Notably, the dCA2-vCA1d projection contributed to the memory formation of object location but not identity. Furthermore, optogenetic inhibition of the dCA2-vCA1d axon terminals reduced fear responses to foot shocks and impaired contextual memory formation. Collectively, our study reveals critical roles of the dCA2-vCA1d circuit in spatial and context-dependent memories, providing new insights into the function of CA2 neurons.