Properties and mechanisms of UP maintenance

Memory is fundamentally important to everyday life, and memory loss has devastating consequences to individuals and society. Understanding the neurophysiological and cellular basis of memory paves the way for gaining insights into the molecular steps involved in memory formation, thereby revealing potential therapeutic targets for neurological diseases. For three decades, long-term potentiation (LTIP) has been the gold standard synaptic model for mammalian memory mechanisms, in large part because of its long-lasting nature. Here, the authors summarize the characteristics of LTP persistence in the dentate gyrus of the hippocampus, comparing this with other hippocampal subregions and neocortex. They consider how long LTP can last and how its persistence is affected by subsequent behavioral experiences. Next, they review the molecular mechanisms known to contribute to LTP induction and persistence, in particular the role of new gene expression and protein synthesis and how they may be associated with potential structural reorganization of the synapse. A temporal schema for the processes important for consolidating LTP into a persistent form is presented. The parallels between the molecular aspects of LTIP and memory strongly support the continuation with LTP as a model system for studying the mechanisms underlying long-term memory consolidation and retention.