Synaptic architecture of a memory engram in the mouse hippocampus
Marco Uytiepo, Yongchuan Zhu, Eric A. Bushong, Katherine Chou, Filip S. Polli, Elise E. Zhao, Keunyoung Kim, Danielle Luu, Lyanne Chang, Dong Uk Yang, Tsz Ching, M.-J. Kim, Yuting Zhang, Grant Walton, Tom Quach, Matthias G. Haberl, Luca Patapoutian, Arya Shahbazi, Yuxuan Zhang, Elizabeth Beutter, Weiheng Zhang, Brian Dong, Aram El Khoury, A. Gu, Elle McCue, Lisa Stowers, Mark H. Ellisman, Anton Maximov
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.