Marco Uytiepo†, Yongchuan Zhu†, Eric Bushong, Katherine Chou, Filip Souza Polli, Elise Zhao,Keun-Young Kim, Danielle Luu, Lyanne Chang, Dong Yang, Tsz Ching Ma, Mingi Kim, Yuting Zhang,Grant Walton, Tom Quach, Matthias Haberl, Luca Patapoutian, Arya Shahbazi, Yuxuan Zhang,Elizabeth Beutter, Weiheng Zhang, Brian Dong, Aureliano Khoury, Alton Gu, Elle McCue, Lisa Stowers,Mark Ellisman, Anton Maximov. Synaptic architecture of a memory engram in the mouse hippocampus. Science 387,eado8316(2025).DOI:10.1126/science.ado8316

Abstract

“Memory engrams are formed through experience-dependent plasticity of neural circuits, but their detailed architectures remain unresolved. Using three-dimensional electron microscopy, we performed nanoscale reconstructions of the hippocampal CA3-CA1 pathway after chemogenetic labeling of cellular ensembles recruited during associative learning. Neurons with a remote history of activity coinciding with memory acquisition showed no strong preference for wiring with each other. Instead, their connectomes expanded through multisynaptic boutons independently of the coactivation state of postsynaptic partners. The rewiring of ensembles representing an initial engram was accompanied by input-specific, spatially restricted upscaling of individual synapses, as well as remodeling of mitochondria, smooth endoplasmic reticulum, and interactions with astrocytes. Our findings elucidate the physical hallmarks of long-term memory and offer a structural basis for the cellular flexibility of information coding.”

Marco Uytiepo†, Yongchuan Zhu†, Eric Bushong, Katherine Chou, Filip Souza Polli, Elise Zhao,Keun-Young Kim, Danielle Luu, Lyanne Chang, Dong Yang, Tsz Ching Ma, Mingi Kim, Yuting Zhang,Grant Walton, Tom Quach, Matthias Haberl, Luca Patapoutian, Arya Shahbazi, Yuxuan Zhang,Elizabeth Beutter, Weiheng Zhang, Brian Dong, Aureliano Khoury, Alton Gu, Elle McCue, Lisa Stowers,Mark Ellisman, Anton Maximov. Synaptic architecture of a memory engram in the mouse hippocampus. Science 387,eado8316(2025).DOI:10.1126/science.ado8316