The Dorsal CA2 to Ventral CA1 Circuit Contributes to Spatial and Context-Dependent Memories
Ning Li1,2 · Bingqing Zhao1 · Xiaowen Shen1 · Hua He3 · Jianxiang Zhou1 · Jing Zhang2 · Lin Xu4 · Xiaochun Chen2 · Chun Xu1,5,6,7
1 Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China
2 Department of Neurology, Fujian Medical University Union Hospital, Fujian Key Laboratory of Molecular Neurology and Institute of Neuroscience, Fujian Medical University, Fuzhou 350004, China
3 Department of Neurosurgery, Third Affiliated Hospital of Navy Military Medical University, Shanghai 200438, China
4 Laboratory of learning and Memory, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
5 Key Laboratory of Brain Cognition and Brain‑inspired Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China
6 China-Hungary Belt-and-Road Joint Laboratory on Brain Science, Shanghai 200031, China
7 University of the Chinese Academy of Sciences, Beijing 100049, China
Abstract
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.
Keywords
Spatial memory; Contextual memory; Hippocampus; CA2; Longitudinal circuit; Single-neuron projectome; Fiber photometry; Optogenetics
