Compensatory Contextual Fear Memory Pathways Develop in the Infralimbic Cortex within 3 Days after the First Test in...

The dorsal hippocampus (DH) is primarily involved in the formation of contextual fear-conditioned (CxFC) memory. However, CxFC memory can be formed even in the absence of the DH. In addition to the DH, the infralimbic cortex (IL), a sub-region of the medial prefrontal cortex (mPFC), also plays an important role in the consolidation of CxFC memory. However, role of IL in the development of compensatory CxFC memory is not known. Here, we have examined (a) the development of the compensatory circuitry of CxFC memory within 3 days after the first test in the absence of the DH and (b) the role of IL in the induction of compensatory CxFC memory in the absence of the DH. The DH-lesioned rats re-trained for CxFC 1 day after the first testing exhibited significantly less freezing compared to the control group. However, the DH-lesioned rats, re-trained for CxFC 3 days after the first testing, showed a robust freezing response. It suggests that the fully functional compensatory circuitry of contextual fear memory develops after multiple training separated by 3 days. Furthermore, we observed that reversible inactivation of the IL of the DH-lesioned rats during the first training waned the formation of compensatory CxFC. It suggests that (a) the IL receives contextual fear memory information during the first trial in the absence of the DH and (b) perturbation in fear memory information encoding in the IL during the first trial impairs the development of the compensatory network in the absence of the DH.