The Quest for the Hippocampal Memory Engram: From Theories to Experimental Evidence

More than a century after Richard Semon's theoretical proposal of the memory engram, technological advancements have finally enabled experimental access to engram cells and their functional contents. In this review, we summarize theories and their experimental support regarding hippocampal memory engram formation and function. Specifically, we discuss recent advances in the engram field which help to reconcile two main theories for how the hippocampus supports memory formation: The Memory Indexing and Cognitive Map theories. We also highlight the latest evidence for engram allocation mechanisms through which memories can be linked or separately encoded. Finally, we identify unanswered questions for future investigations, through which a more comprehensive understanding of memory formation and retrieval may be achieved.