The technology has changed and with it some of the questions that can be tackled more successfully. But has the evolution of methods, concepts, and data blended with creativity to advance the character of memory research in the past 25 years? Our view is that they are doing so, and we now reflect on the future implications of the current state of the art. We attempt to chart patches of the changed terrain of the science of memory and how it has changed and propose a few idiosyncratic conclusions on where it might be going. Psychological conceptions of learning and memory have long distinguished the acquisition or “encoding” process, from that of “trace storage” and

the subsequent processes of “consolidation” that somehow Etoposide clinical trial enable storage to be lasting. Efforts to translate these concepts into the neurobiological domain distinguish the Afatinib in vitro very rapid events associated with memory

encoding in one-shot learning, such as activation of the glutamate NMDA receptor in neurons of the hippocampus, with those associated with the subsequent creation of biophysical, biochemical, or structural changes thought to mediate lasting trace storage. A memory “trace” or “engram” is a hypothetical entity that refers to physical changes in the nervous system that outlast the stimulus. However, while the trace may be created and sustained for a while, that is no guarantee that it will last. All too often, as in long-term potentiation decaying back to “baseline” levels, experience-induced perturbations of structure and function are short lasting. However, a key idea was that a consolidation process can be engaged to enable these physical changes to be sustained GBA3 and then to last indefinitely (McGaugh, 1966). Specifically,

much of the research in the neuroscience of memory in the past century was embedded in the conceptual framework of a “dual-trace” model (Hebb, 1949): a short-term trace, which dissipates rapidly unless converted by consolidation into a long-term trace. It was generally thought that consolidation occurs just once per item and that the long-term trace would be stable and essentially permanent unless the areas of the brain that store the memory were damaged or the ability to retrieve the information somehow impaired. This conceptual framework was strongly influenced by the view that the neurobiological mechanisms of consolidation and maintenance of long-term memory are similar or even identical to those operating in tissue development, in which the cells become committed to their fate for the rest of their life unless struck by an injury or pathology. Indeed, much in the models and terminology of the highly successful molecular neurobiology of memory (Kandel, 2001) resonates with the reductionist world of the molecular biology of development.