Scientific Understanding of Consciousness
Long-Term Memory Formation
Science 18 February 2011: Vol. 331 no. 6019 pp. 924-928
Edith Lesburguères, Oliviero L. Gobbo, Stéphanie Alaux-Cantin, Anne Hambucken, Pierre Trifilieff, and Bruno Bontempi
Institut des Maladies Neurodégénératives, CNRS UMR 5293, Universités Bordeaux 1 et 2, Avenue des Facultés, 33405 Talence, France.
Although formation and stabilization of long-lasting associative memories are thought to require time-dependent coordinated hippocampal-cortical interactions, the underlying mechanisms remain unclear. Here, we present evidence that neurons in the rat cortex must undergo a “tagging process” upon encoding to ensure the progressive hippocampal-driven rewiring of cortical networks that support remote memory storage. This process was AMPA- and N-methyl-d-aspartate receptor–dependent, information-specific, and capable of modulating remote memory persistence by affecting the temporal dynamics of hippocampal-cortical interactions. Post-learning reinforcement of the tagging process via time-limited epigenetic modifications resulted in improved remote memory retrieval. Thus, early tagging of cortical networks is a crucial neurobiological process for remote memory formation whose functional properties fit the requirements imposed by the extended time scale of systems-level memory consolidation.
Memories for facts and events are not acquired in their definitive form but undergo a gradual process of stabilization over time. According to the so-called standard theory of systems-level memory consolidation, the hippocampus (HPC) is believed to integrate, in the form of an anatomical index, information transmitted from distributed cortical networks that support the various features of a whole experience. Upon encoding, the HPC rapidly fuses these different features into a coherent memory trace. Consolidation of this new memory trace at the cortical level would then occur slowly via repeated and coordinated reactivation of hippocampal-cortical networks in order to progressively increase the strength and stability of cortical-cortical connections that represent the original experience. Over days to weeks as memories mature, the role of the HPC would gradually diminish, presumably leaving cortical areas to become capable of sustaining permanent memories and mediating their retrieval independently. Using brain imaging, we have provided evidence supporting the time-limited role of the HPC as a consolidation organizing device of remote memory in the cortex. Yet the nature and dynamics of plasticity phenomena as well as the neuronal constraints within hippocampal-cortical networks responsible for the formation of remote memories have remained elusive.
Replay of encoding-related activity during phases of sleep has emerged as a core mechanism for driving structural changes within hippocampal-cortical neuronal networks. In this context, our findings identify early tagging of cortical networks as a crucial process for the formation of enduring memories and suggest that synaptic tags contribute actively, although not exclusively, to the development but also the maintenance of this form of plasticity in the cortex. The identity of synaptic tags needs to be further explored, although potential candidates have started to emerge. Given the complex nature of memory traces that typically integrate the various modalities of an event, it is likely that a plethora of synaptic molecules act in concert to capture the various patterns of synaptic activity elicited upon encoding. These tags may then be recruited differentially during the course of systems-level consolidation depending on the status of existing knowledge in the cortex.
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