Memory traces bias new learning for hippocampal generalization

Generalizing prior experience to guide behavior in novel situations is a fundamental cognitive function, yet how this occurs remains poorly understood. Here we combined longitudinal imaging in mice with modeling and circuit perturbation to examine generalization in hippocampal CA1 across environments with shared task structure. Prior training accelerated behavioral adaptation and preserved cross-environment representations. We identified putative memory traces associated with generalization. At the cellular level, spatially informative residual activity reflecting generalizable information biased which neurons formed place fields (PFs) and where via behavioral timescale synaptic plasticity (BTSP). At the population level, BTSP was associated with rapid alignment of novel-environment network dynamics to familiar neural subspaces. Chemogenetic suppression of local CA1 during training reduced residual activity, BTSP induction, place cell recruitment and generalization. In sum, the influence of memory traces on new PF formation may allow past experience to guide new learning to form representations based on generalizable features.