CONTEXTUAL MEMORY RETENTION, GENERALIZATION, AND RETRIEVAL-INDUCED C-FOS EXPRESSION IN MICE OVER LONG PERIODS OF TIME

Systems consolidation is a gradual redistribution of memory from hippocampus to cortical networks. However, long-term dynamics and neural substrates of such process remain insufficiently understood. We asked how long such memories can persist in mice without explicit retrieval, and how training intensity affects retention, generalization, and c-Fos expression during memory retrieval. Male C57BL/6J mice were subjected either to standard contextual fear conditioning (1×2 s, 1.0 mA) or high-intensity footshock protocol (3×10 s, 1.5 mA); controls received no shock. Independent groups were tested from 1 day to 6 months after training; generalization was assessed in another context for up to 12 months. For molecular readout mice were euthanised 90 min after test for recall; c-Fos+ cells were quantified in CA1, CA3, dentate gyrus (DG) and retrosplenial cortex. Standard training produced a non-monotonic retention curve: freezing strengthened to a peak at ~2-4 weeks, remained elevated at 2 months, then fell to control levels by 6 months. High-intensity training resulted in high freezing during conditioning and memory retrieval sessions ut to 2 months, with residual memory remaining at 6 months. Generalization was minimal after standard training, was pronounced after high-intensity training, and attenuated over 3-12 months. Memory retrieval elicited the strongest c-Fos activation in the CA1 and retrosplenial cortex, with a subsequent increase in the DG at 6 months. Our results indicate a prolonged memory maturation phase and dissociation between involvement of neural circuit and behavior. Supported by the Non-commercial Foundation for Support of Science and Education “INTELLECT”.