Investigating the Transition from Recent to Remote Memory Using Advanced Tools

Remote memories, weeks to decades long, are usually the ones most important to the organism, as the longevity of a memory is tightly connected to its significance. Retrograde amnesia studies in human patients as well as lesions and immediate early gene expression investigation in animal models, suggested that the hippocampus has a time dependent role in memory consolidation. Namely, that as a memory matures it becomes independent of the hippocampus and instead depends on extra-hippocampal areas. However, accumulating evidence implies that this temporal segregation is not as rigid as originally proposed. In this review we will focus on the integration of new methods, such as chemogenetics, optogenetics and calcium imaging, which enable genetic specificity as well as high temporal and spatial resolution. Using these methods, recent studies have started to resolve the inconsistencies of past findings by observing and manipulating neural ensembles in different brain regions. We then discuss how these techniques can be applied to investigate the cellular underpinnings of memory across multiple time points, and employed to study the contribution of various cell types to remote memory.