Multiple Stages of Memory Formation and Persistence

The idea that memories are not made instantly after learning but need to undergo a time-dependent, metabolically active complex consolidation process before they can be stably stored has dominated the neuroscience of learning and memory for decades. Based mostly on pharmacological and lesion data, and deeply intertwined with the notion that mechanisms of synaptic plasticity such as long-term potentiation and long-term depression are not mere epiphenomena but the physiological foundations of learning, the consolidation hypothesis has encouraged, framed, and dominated more than 50 years of research and debate on the localization and migration of the mnemonic trace as well as about the rhythm and speed of its formation. In the meantime, we have seen the emergence of different models proposing the existence of several memory phases and intermediate stages to explain the increasingly complex scenario of overlapping biochemical and behavioral processes governing memory storage, as well as alternative viewpoints that directly confront with the central tenets of the consolidation hypothesis. Here, we will review some of those models and discuss the major challenges faced by the field in its quest to uncover the basis of memory persistence.