Engram neurons: Encoding, consolidation, retrieval, and forgetting of memory.

Tremendous strides have been made in our understanding of the neurobiological substrates of memory - the so-called memory "engram". Here, we integrate recent progress in the engram field to illustrate how engram neurons transform across the "lifespan" of a memory - from initial memory encoding, to consolidation and retrieval, and ultimately to forgetting. To do so, we first describe how cell-intrinsic properties shape the initial emergence of the engram at memory encoding. Second, we highlight how these encoding neurons preferentially participate in synaptic- and systems-level consolidation of memory. Third, we describe how these changes during encoding and consolidation guide neural reactivation during retrieval, and facilitate memory recall. Fourth, we describe neurobiological mechanisms of forgetting, and how these mechanisms can counteract engram properties established during memory encoding, consolidation, and retrieval. Motivated by recent experimental results across these four sections, we conclude by proposing some conceptual extensions to the traditional view of the engram, including broadening the view of cell-type participation within engrams and across memory stages. In collection, our review synthesizes general principles of the engram across memory stages, and describes future avenues to further understand the dynamic engram.