Multiscale Mechanisms of Memory: From Synapses to Systems

Han Hao

doi:10.54254/2753-8818/2025.AU25942

Theoretical and Natural ScienceOpen access

Multiscale Mechanisms of Memory: From Synapses to Systems

Research Article

Open Access

Multiscale Mechanisms of Memory: From Synapses to Systems

Han Hao ^1*

¹ University of Wisconsin–Madison

^*Corresponding author: hhao27@wisc.edu

Published on 13 August 2025

TNS Vol.124

ISSN (Print): 2753-8826

ISSN (Online): 2753-8818

ISBN (Print): 978-1-80590-271-3

ISBN (Online): 978-1-80590-272-0

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Abstract

Learning and memory arise from biochemical events taking place in nanometre‑sized synaptic compartments and scale up to coordinated activity patterns that span the whole brain. Classical models of memory focused on N‑methyl‑d‑aspartate‑receptor (NMDAR)–dependent long‑term potentiation (LTP) and long‑term 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 scales—molecules, synapses, circuits, networks, and technologies—highlighting 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 Alzheimer’s disease and post‑traumatic stress disorder. By unifying molecular insight with systems‑level interrogation and AI‑assisted neural decoding, we outline a roadmap toward a predictive, multiscale science of memory.

Keywords:

Engram, Plasticity, Integration, Neuroscientific Techniques, Memory Therapy

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