Multiple context discrimination in adult rats: sex variability and dynamics of time-dependent generalization of an aversive memory

Memory generalization involves the transfer of conditioned fear responses to novel contexts, a phenomenon observed in systems consolidation, whereby a time-dependent reduction in discrimination precision occurs due to the reorganization of brain regions supporting memory retrieval. To understand the fine temporal structure of this process across sexes, young adult female and male rats were trained in contextual fear conditioning and tested in the same or one of three distinct novel contexts at 2, 28 or 45 days post-training. Neutral contexts were designed to allow graded levels of fear expression relative to the training context, and sex differences were evident at the recent memory test. This pattern, however, disappeared over time due to partial generalization, with fear converging into similar, higher values, grouped into two levels for both sexes. In all experiments, females were better discriminators and displayed lower fear responses than males, apparently prioritizing different sensory modalities, with multivariate analysis suggesting that chamber size was salient for females and floor texture for males. This study is the first to compare fear responses between adult female and male rats across multiple neutral contexts and timepoints revealing several dimorphic findings.