The lateralization of left hippocampal CA3 during the retrieval of spatial working memory

Da Song,Deheng Wang,Yan Yan,Zhen Xie,Tianyi Yan,Zhenzhen Quan,Chunjian Wang,Qing Shi,Yanhui Li,Yuchen Liu,Yili Wu,Ke Zhang ,Tao Huang,Yiran Lang,Zhe Wang,Juan Zhao,Talal Jamil Qazi,Heao Zhang,Qinghu Yang,Hong Qing

doi:10.1038/s41467-020-16698-4

Abstract

The hippocampal CA3 contributes to spatial working memory (SWM), but which stage of SWM the CA3 neurons act on and whether the lateralization of CA3 function occurs in SWM is also unknown. Here, we reveal increased neural activity in both sample and choice phases of SWM. Left CA3 (LCA3) neurons show higher sensitivity in the choice phase during the correct versus error trials compared with right CA3 (RCA3) neurons. LCA3 initiates firing prior to RCA3 in the choice phase. Optogenetic suppression of pyramidal neurons in LCA3 disrupts SWM only in the choice phase. Furthermore, we discover that parvalbumin (PV) neurons, rather than cholinergic neurons in the medial septum (DB were cholinergic neurons), can project directly to unilateral CA3. Selective suppression of PV neurons in the MS projecting to LCA3 impairs SWM. The findings suggest that MSPV-LCA3 projection plays a crucial role in manipulating the lateralization of LCA3 in the retrieval of SWM.

Highlights

The hippocampal CA3 contributes to spatial working memory (SWM), but which stage of SWM the CA3 neurons act on and whether the lateralization of CA3 function occurs in SWM is unknown
The hippocampal CA3-CA1 pyramidal neuron synapses are revealed asymmetrical that inputs from right CA3 (RCA3) to CA1 possess larger and more perforated postsynaptic densities and GluR1 expression than that from Left CA3 (LCA3), and the lateralization of right hippocampus is further functionally implicated to be responsible for improving the accuracy of spatial memory in animal behavioral tests[11,12]
We demonstrate that selective suppression of MSPV-LCA3 projecting neurons impairs the performance of SWM in the choice phase

Summary

Introduction

The hippocampal CA3 contributes to spatial working memory (SWM), but which stage of SWM the CA3 neurons act on and whether the lateralization of CA3 function occurs in SWM is unknown. The hippocampal CA3-CA1 pyramidal neuron synapses are revealed asymmetrical that inputs from RCA3 to CA1 possess larger and more perforated postsynaptic densities and GluR1 expression than that from LCA3, and the lateralization of right hippocampus is further functionally implicated to be responsible for improving the accuracy of spatial memory in animal behavioral tests[11,12]. Whether the hippocampal CA3 neurons from left to right hemisphere have asymmetrical firing patterns in the working memory process and whether the lateralization is regulated by upstream projecting region to CA3 is still unknown. LCA3 and RCA3 neurons exhibit asymmetrical amplitudes of the increased neural activity in the choice phase during the correct versus the error trials. We demonstrate that selective suppression of MSPV-LCA3 projecting neurons impairs the performance of SWM in the choice phase

Methods

Results

Conclusion