Contextual Fear Conditioning Induces Activity-Dependent Gene Expression in the Dorsal but not in the Ventral Hippocampus

The hippocampus, a key structure playing an important role in contextual fear-conditioning (CxFC), shows functional specialization along its dorsoventral axis. The dorsal hippocampus is primarily implicated in spatial and contextual processing, whereas the ventral hippocampus is more closely associated with affective and emotional regulation. In this study, we examined whether CxFC selectively engages activity-dependent gene expression in the dorsal hippocampus (DH) but not in the ventral hippocampus (VH). Mice were subjected to CxFC, and freezing behavior across baseline, training, and testing sessions was evaluated. Molecular analyses were conducted to assess the temporal expression patterns of Arc and c-Fos proteins in the DH and VH at 0, 1, 3, and 5 hours on conditioning and post-conditioning days. Fear-conditioned animals displayed a significant increase in freezing behavior during the testing session compared to baseline, indicating strong fear memory retention. Arc expression in the DH showed a time-dependent increase, peaking at the 1st hour and remained highly expressed till the 5th hour on conditioning and post-conditioning days. No significant changes were observed in the VH. Similarly, c-Fos expression in the DH increased significantly at 1st, 3rd, and 5th hours on conditioning and post-conditioning days, while no significant activation was detected in the VH. These findings demonstrate that contextual fear conditioning selectively activates the DH, as evidenced by upregulation of Arc and c-Fos expression. The VH did not show corresponding molecular changes, suggesting a region-specific role of the DH and VH in the consolidation fear memory.