The functional disconnection of the dorsal hippocampus and prelimbic cortex impairs the contextual fear conditioning of stimuli separated in time in male rats.

The hippocampus plays a fundamental role in contextual fear conditioning (CFC). Studies have found that its ventral portion is mostly related to emotional processing, while the dorsal portion is related to the processing of contextual memories. The prelimbic cortex (PL) is also associated with contextual fear conditioning with temporal discontinuity (CFC-5s), in which a brief time gap separates context exposure and the aversive stimulus. Studies have shown that PL is involved in tasks that require the maintenance of information over short time intervals, such as working memory. The aim of the present study is to verify whether pharmacological manipulations of the dorsal hippocampus (dHPC) unilaterally in conjunction with contralateral inactivation of the PL interfere with the acquisition of CFC-5s. For this, Male Wistar rats were divided into three groups: asymmetric manipulation (CONTRA), ipsilateral manipulation (IPSI) and saline administration (SALINE). In Experiment 1, AP5 was infused into the dHPC and muscimol into the PL; in Experiment 2, muscimol was infused into both regions. Rats were trained and tested to a contextual fear conditioning protocol with temporal discontinuity. The results show that infusion of AP5 in the dorsal hippocampus impairs CFC-5s, whereas muscimol infusion does not. These findings indicate that NMDA receptor-dependent plasticity in the dHPC, rather than transient neural activity, is critical for the interaction between dHPC and PL during the acquisition of temporally discontinuous contextual memories.