Engram mechanisms of memory linking and identity

Memories are thought to be stored in neuronal ensembles referred to as engrams. Studies have suggested that when two memories occur in quick succession, a proportion of their engrams overlap and the memories become linked (in a process known as prospective linking) while maintaining their individual identities. In this Review, we summarize the key principles of memory linking through engram overlap, as revealed by experimental and modelling studies. We describe evidence of the involvement of synaptic memory substrates, spine clustering and non-linear neuronal capacities in prospective linking, and suggest a dynamic somato-synaptic model, in which memories are shared between neurons yet remain separable through distinct dendritic and synaptic allocation patterns. We also bring into focus retrospective linking, in which memories become associated after encoding via offline reactivation, and discuss key temporal and mechanistic differences between prospective and retrospective linking, as well as the potential differences in their cognitive outcomes. Many cognitive functions rely on the ability to link distinct but related memories, while retaining the capacity to recall the individual details of the linked memories. Inokuchi and colleagues describe evidence that memory linking involves engram overlap and discuss the mechanisms that regulate this process.