Associative memory formation reshapes the learning trajectory of a novel cognitive map

Abstract

Learning never occurs on a blank slate, as each experience an animal encounters in its daily life is encoded by circuits already shaped by previous ones. During such experiences, the hippocampus builds place-cell-based cognitive maps of the environments explored, and encodes ensemble-based memories for associations among events that occur within them. These spatial and mnemonic representations draw on neurons embedded within the same network. However, whether forming an associative memory of an experience unfolding in one context changes how the same hippocampal network maps a different one is unknown. Here, we longitudinally imaged CA3 neurons as mice familiarized with one environment, encoded either an associative fear memory or a context-only memory in a different environment, and then explored a novel one. Across separate experiences, neuronal recruitment into cognitive maps and memory ensembles followed structured, partially orthogonal allocation rules that were consistent across fear and neutral memories, with ensemble membership and place-cell identity showing no reciprocal enrichment. Fear memory encoding left the properties of the familiar map unchanged, while altering those of the novel one. From first exposure, the novel map already recruited a familiar-like fraction of place cells and supported spatial decoding with near-familiar precision, and its population activity occupied a latent subspace that aligned with the familiar map while remaining context-specific. Yet this novel map failed to undergo the experience-dependent refinement of decoding precision and across-day latent alignment that normally accompanies familiarization, even though place cells continued to gain spatial information and to remap. Associative memory encoding therefore shifts CA3 into a distinct representational regime, decoupling the immediate precision of a new cognitive map from the experience-dependent refinement of its context-specific population embedding.