Dentate gyrus drives pattern separation in proximal CA3 during rate, but not global, remapping

Pattern separation converts overlapping experiences into discrete memory traces, with granule-cell sparsity in the dentate gyrus (DG) thought to execute this computation. Proximal CA3 is functionally aligned with the DG through dense reciprocal connectivity, yet the manner in which DG output governs pattern separation within proximal CA3 remains unresolved. This study combined selective DG lesions with high-resolution recordings across the CA3 while rats explored environments that varied in contextual similarity. Global remapping in CA3 remained largely intact following DG lesion, but rate remapping was almost entirely abolished. Discrimination impairments were most pronounced in proximal CA3 and attenuated along the transverse axis toward distal CA3, paralleling the topography of mossy-fiber projections. These data support a hierarchical and mode-specific framework for pattern separation: the entorhinal cortex selects between global and rate remapping according to input dissimilarity, while the DG selectively enhances discrimination of similar inputs via rate-based modulation. This mechanism clarifies how the entorhinal-hippocampal circuit resolves overlapping experiences into distinct memory representations.