Multiscale Mechanisms of Memory: From Synapses to Systems

Learning and memory arise from biochemical events taking place in nanometresized synaptic compartments and scale up to coordinated activity patterns that span the whole brain. Classical models of memory focused on Nmethyldaspartatereceptor (NMDAR)dependent longterm potentiation (LTP) and longterm depression (LTD), treating these synaptic mechanisms as the molecular currency of information storage. However, new discoveries over the past two decades have compelled adoption of a broader, multiscale view of memory. This perspective integrates glial modulation, dynamic neuronal ensembles (engrams), oscillatory brain states, and advanced neurotechnologies. This review synthesises advances across five nested scalesmolecules, synapses, circuits, networks, and technologieshighlighting how mechanisms at each level both constrain and enable those above and below. Throughout, we contrast past dogma with new evidence, identify unresolved gaps, and discuss translational opportunities for disorders such as Alzheimers disease and posttraumatic stress disorder. By unifying molecular insight with systemslevel interrogation and AIassisted neural decoding, we outline a roadmap toward a predictive, multiscale science of memory.