The cortical structure of consolidated memory: A hypothesis on the role of the cingulate–entorhinal cortical connection

• Converging evidence points to essential roles of the cingulate and entorhinal cortices in consolidated memory.
• Anatomical connectivity patterns between cingulate and entorhinal cortices are consistent with a role in long-term memory.
• Observations related to neural coding and plasticity suggest that plastic changes in these areas are memory-specific.
• We offer several experimental predictions consistent with the hypothesis that connections between cingulate and entorhinal cortex hold initially hippocampal-dependent memories in the long-term.

Daily experiences are represented by networks of neurons distributed across the neocortex, bound together for rapid storage and later retrieval by the hippocampus. While the hippocampus is necessary for retrieving recent episode-based memory associations, over time, consolidation processes take place that enable many of these associations to be expressed independent of the hippocampus. It is generally thought that mechanisms of consolidation involve synaptic weight changes between cortical regions; or, in other words, the formation of “horizontal” cortico-cortical connections. Here, we review anatomical, behavioral, and physiological data which suggest that the connections in and between the entorhinal and cingulate cortices may be uniquely important for the long-term storage of memories that initially depend on the hippocampus. We propose that current theories of consolidation that divide memory into dual systems of hippocampus and neocortex might beimproved by introducing a third, middle layer of entorhinal and cingulate allocortex, the synaptic weights within which are necessary and potentially sufficient for maintaining initially hippocampus-dependent associations over long time periods. This hypothesis makes a number of still untested predictions, and future experiments designed to address these will help to fill gaps in the current understanding of the cortical structure of consolidated memory.