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bioRxiv · 10.64898/2025.12.04.692471

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

Hu, S.-Y.·Duan, Y.-L.·Long, J.-L.·Cai, X.·Lu, L.
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Abstract

The dentate gyrus (DG) transforms overlapping experiences into discrete memory traces, yet how DG output shapes population coding within the hippocampus remains unclear. We combined selective DG lesions with large-scale recordings across the CA3 proximo-distal axis as rats explored environments varying in contextual similarity. Global remapping in CA3 remained robust following DG lesion, whereas rate-based contextual coding was substantially attenuated, most strongly in proximal CA3 and attenuating distally, paralleling mossy-fiber topography. Granule cells and mossy cells additionally coded complementary aspects of local objects and mediated CA3 responses to object manipulation. These data causally link the enhanced rate coding of proximal CA3 to its preferential DG innervation and support a dual organization of contextual discrimination: categorical changes in environmental identity are signaled independently of the DG, whereas fine-grained discrimination is facilitated by DG-mediated rate modulation. By selectively amplifying rate-coded discrimination of subtle contextual differences, the DG sharpens the hippocampal network's capacity to resolve overlapping experiences into distinct representations.

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Hu, S.-Y., Duan, Y.-L., Long, J.-L., Cai, X., Lu, L.. 2025-12-09. Dentate gyrus drives pattern separation in proximal CA3 during rate, but not global, remapping. https://doi.org/10.64898/2025.12.04.692471

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