Distinct roles of medial prefrontal cortex subregions in the consolidation and recall of remote spatial memories

It is a common believe that memories with time become progressively independent of the hippocampus and are gradually stored in cortical areas. This view is mainly based on evidence demonstrating an impairing effect of prefrontal cortex (PFC) manipulations in the retrieval of remote memories paralleled by a lack of effect of hippocampal inhibition. What is more controversial is whether activity in the mPFC is required immediately after learning to initiate the consolidation process. Further question are possible functional differences among the subregions of the PFC in the formation and storage of remote memories. To address these issues, we directly contrasted the effects of loss-of-function manipulations of the the anterior cingulate cortex (aCC) and the ventro-medial prefrontal cortex (vmPFC), that includes the infralimbic and the prelimbic cortices, before testing, and immediately after training, on the ability of CD1 mice to recall the location of the hidden platform in the Morris water maze. To this aim we injected in the vmPFC or in the aCC an AAV carrying the hM4Di receptor. Interestingly, pre-test administrations of clozapine-N-oxide (CNO) revealed that the aCC, but not the vmPFC, is necessary to recall remote spatial information. Furthermore, systemic post-training administration of CNO (3mg/kg) impaired memory recall at remote time points but not recent time points in both experimental groups. Overall, these findings revealed a functional dissociation between the two prefrontal areas, demonstrating that they are both involved in the early consolidation of remote spatial memories, but that only the aCC is engaged in their recall. Significant statementThe PFC constitute an heterogeneous brain region from both a neuroanatomical and a functional point of view in which at least two main component can be distinguished: the vmPFC, with extensive connections with the limbic system and the HPC and the aCC characterized by its reciprocal connections with the sensorimotor cortex (Heidbreder and Groenewegen, 2003; Uylings et al., 2003; Le Merre et al., 2021). Contrasting the two components of the PFC, the aim of this study was twofold: investigate their relative contribution to the recall of remote spatial memory and in the consolidation of both recent and remote memories. The results demonstrated an interesting dissociation between the two components. Loss-of-function manipulation of the aCC but not the vmPFC impaired recall of remote spatial memory, however, both subdivisions contributed to its consolidation.