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

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 MS PV -LCA3 projection plays a crucial role in manipulating the lateralization of LCA3 in the retrieval of SWM. The CA3 region of the hippocampus is involved in spatial working memory. Here, the authors show that neurons in the left CA3 are more active in the choice phase of correct trials of spatial working memory than neurons in the right CA3, revealing lateralization of spatial working memory.