Neurobiology of systems memory consolidation.

Psychological theories posit that the hippocampus rapidly forms associations among ongoing events as they unfold. During a subsequent maturation process, so-called systems memory consolidation, these associations are gradually stabilized within distributed neocortical circuits through close interactions between the hippocampus and neocortex. In the past 50 years, a major effort in neurobiological research has been directed towards translating these descriptive accounts into tangible, biological processes in the brain. Until the early 2000s, most studies exclusively focused on examining whether the hippocampus becomes unnecessary for memory retrieval once the memory has been consolidated. With recent methodological advances, however, the field shifted attention to several other theoretical accounts and began to uncover the genetic, physiological and structural underpinnings of systems memory consolidation at an unprecedented level of precision. Here I review these neurobiological findings in the past 15 years within a framework of six essential predictions extracted from the psychological theories. Genetic approaches have made it possible to tag neurons that were activated during memory encoding and investigate their physiological and genetic profiles as well as reactivation patterns during subsequent retrieval. In parallel, electrophysiological and imaging approaches detected signs of the gradual refinement of memory representations and its underlying hippocampal-neocortical dialogue in millisecond-resolved neural firing patterns, the inter-region coupling of neural activity, across-day stability of neural ensemble activity and functional connectome. This summary represents substantial progress in our understanding of neurobiological mechanisms of systems memory consolidation whilst also identifying several essential remaining questions for future investigations.