From creation to consolidation: a novel framework for memory processing.

Long after playing a game of squash or reading this essay, your memory for playing and reading continues to be processed by your brain. These “offline” processes improve your game and your understanding of this essay, and more generally, enhance adaptive behavior. Yet progress in understanding how the brain regulates the offline processing of memories has been hampered by the absence of robust models for interpreting diverse, and often contradictory, experimental results. In the last 20 years, highly fertile quantitative models across the biological spectrum from the molecular to the behavioral have proved critical in advancing our understanding of memory encoding (e.g., [1–5]). But these models have focused upon the exact moment a memory is formed; while our ability to recall an event is dictated, at least in part, by events that precede and follow the encoding of a new memory. The critical role that events following memory encoding play in determining subsequent recall have been recognized for at least the past 100 years [6]. Yet few, if any, models have been formulated for these “offline” processes that produce qualitative and quantitative changes in a memory during consolidation (Box 1). Our attempts to understand these mysterious processes have generated a purely descriptive set of observations. Although these observations have provided critical glimpses into offline memory processing, they have also produced unresolved contradictions between some of the most fundamental and critical sets of observations (for reviews, see [7–11]). Box 1. Memory Consolidation A memory passes through at least three key milestones in its development: initially it is encoded, then it is consolidated, and finally it is retrieved. During consolidation a memory can undergo both quantitative and qualitative changes. A memory may be enhanced, demonstrated by a quantitative increase in performance, or it may be stabilized, demonstrated by becoming quantitatively less susceptible to interference [10,46,47]. A memory can also undergo qualitative changes: there can be a shift in the strategy used to solve a problem or the emergence of awareness for what had earlier been learned [49,50]. Although there is a rich diversity in the behavioral expression of consolidation, each of these examples may rely upon the same underlying computation (see main text). Consolidation is measured as a change in performance between testing and retesting [46,47]. Contrasting final performance at retesting against an initial baseline provides a direct measure of “offline” performance changes that occur during consolidation. For example, one set of observations suggests that consolidation may occur over any time interval, whereas another body of data suggests that these processes require sleep [6,8]. Clearly, both cannot be true. Resolving the inherent conflict between these perspectives strikes at the very heart of how biological mechanisms process memories after their initial encoding. Making sense of what threatens to become an avalanche of disconnected and incoherent empirical findings may require novel theories that can simultaneously reconcile apparently inconsistent observations and provide a fertile, hypothesis-driven framework for future work. Here, drawing upon examples mainly from the processing of motor skill memories, I take the first tentative steps toward assembling such a framework.