Neurobiological mechanisms of forgetting across timescales

Every species in the animal kingdom that learns, also forgets. Despite this balance between learning and forgetting, most neuroscientific explorations of memory have focused on how learning occurs, with recent studies identifying engrams as putative biological substrates for memory. Here we review an emerging literature that, in contrast, explores how our brains forget. These studies reveal that forgetting engages a broad collection of mechanisms that function to reduce engram accessibility. However, changes in accessibility emerge on vastly different timescales. At short timescales, forgetting is modulated by fluctuations in brain states that alter engram accessibility in a moment-to-moment fashion. In the intermediate- and long-term, forgetting depends, in part, on mechanisms that rewire engrams, rendering them gradually harder to access. Viewed this way, forgetting encompasses a family of plasticity mechanisms that modulate engram accessibility, perhaps in order to prioritize those memories that are most timely or relevant to the situation at hand.