biostudies-literatureUnknownJiang ANIMH NIH HHSNINDS NIH HHSCA1 place fields support spatial maps critical for memory, yet how bilateral CA3 inputs shape these maps during learning remains unclear. Using two-photon calcium imaging and optogenetic inhibition in head-fixed mice navigating a virtual track, we examined left and right CA3 projections to right CA1 (CA1_R) as animals familiarized to a novel environment. CA1_R maps were initially inaccurate but stabilized after ~10 laps, defining an early-phase of map refinement followed by a late-phase of stability. During the early-phase, right CA3 inputs predominantly drove refinement, whereas left CA3 inputs controlled stability later. These effects arose at the single-cell level, with right CA3 inputs driving high-amplitude, reliable fields early and left inputs supporting reliable fields later. Axonal recordings revealed a matching shift: right CA3 axons showed greater place-field activity and reliability early, whereas left CA3 axons became more reliable later. Thus, CA3 input dominance transitions from right to left, coordinating CA1_R map refinement and stabilization.bioRxiv : the preprint server for biology2025.10.26.684700https://www.ebi.ac.uk/biostudies/studies/S-EPMC12636601biostudies-literatureLearning-Dependent Shift from Right to Left CA3 Input Dominance Shapes the Evolution of Right CA1 Spatial Maps.PMC12636601RF1 NS127123R21 NS128822DP2 NS111657R01 MH136274GoodSmith DTortolani AFRamirez-Matias JSheffield MEJJiang AfalseLearning-Dependent Shift from Right to Left CA3 Input Dominance Shapes the Evolution of Right CA1 Spatial Maps.CA1 place fields support spatial maps critical for memory, yet how bilateral CA3 inputs shape these maps during learning remains unclear. Using two-photon calcium imaging and optogenetic inhibition in head-fixed mice navigating a virtual track, we examined left and right CA3 projections to right CA1 (CA1_R) as animals familiarized to a novel environment. CA1_R maps were initially inaccurate but stabilized after ~10 laps, defining an early-phase of map refinement followed by a late-phase of stability. During the early-phase, right CA3 inputs predominantly drove refinement, whereas left CA3 inputs controlled stability later. These effects arose at the single-cell level, with right CA3 inputs driving high-amplitude, reliable fields early and left inputs supporting reliable fields later. Axonal recordings revealed a matching shift: right CA3 axons showed greater place-field activity and reliability early, whereas left CA3 axons became more reliable later. Thus, CA3 input dominance transitions from right to left, coordinating CA1_R map refinement and stabilization.2025-01-01T00:00:00Z2025 Oct2026-06-16T03:09:41.66Z2026-06-16T03:06:23.081ZS-EPMC126366014127930910.1101/2025.10.26.684700