Dynamics of Hippocampal-Cortical Interactions During Memory Consolidation: Insights from Functional Brain Imaging

Both clinical studies and experiments in animals have provided evidence for the existence of a temporally graded retrograde amnesia following lesions of the medial temporal lobe, including the hippocampus. This form of amnesia, which is characterized by a loss of memory for recent events acquired prior to the onset of amnesia while more remote memories are preserved, is one of the major arguments for the existence of a consolidation process necessary for stable, long-term memory formation. It is now well established that the formation of declarative memory (memories for facts and events) involves changes in synaptic plasticity within the medial temporal lobe. However, our group and others have demonstrated that the hippocampus has only a time-limited role in long-term memory storage of certain types of information, such that extrahippocampal structures, namely cortical regions, eventually become capable of supporting the retrieval of remote memories independently. In other words, the hippocampus does not store remote memories, yet what happens beyond the hippocampus remains unclear. This issue has been the subject of intense investigation and debate in the field of cognitive neuroscience, but to date, no convincing evidence as to the identity, mechanisms and putative interactions between memory systems underlying remote memory storage and retrieval have clearly emerged. To address this issue, we have conducted brain imaging experiments using (14C)2-deoxyglucose mapping and analyses of changes in the expression of activity-dependent genes (c-fos and Zif268) in mice submitted to recent and remote spatial memory testing. Our findings show that memory processing and consolidation require a time-dependent hippocampal-cortical dialogue, ultimately enabling structured cortical networks to mediate recall and use of cortically stored remote memories independently. However, the cortex does not simply serve as a passive storage site but may also actively integrate new memories depending on the organization and status of pre-existing knowledge. The prefrontal cortex in particular appears to play a crucial role in integrating and binding information from distributed cortical networks and in modulating the level of hippocampal activation during memory recall. These findings are discussed in the context of current models of memory consolidation and in light of data from the recent literature in humans and animals.