Synaptic architecture of a memory engram in the mouse hippocampus
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.
Authors
- Filip S. Polli (ORCID: https://orcid.org/0000-0002-3854-9918)
- Weiheng Zhang (ORCID: https://orcid.org/0000-0002-1710-0249)
- A. Gu
- Marco Uytiepo (ORCID: https://orcid.org/0009-0005-1615-130X)
- Anton Maximov (ORCID: https://orcid.org/0000-0001-6186-4572)
- Elizabeth Beutter (ORCID: https://orcid.org/0000-0002-3854-7381)
- Danielle Luu
- Ali Shahbazi (ORCID: https://orcid.org/0000-0001-5222-4792)
- Mark H. Ellisman (ORCID: https://orcid.org/0000-0001-8893-8455)
- Gerald Walton
- Matthias G. Haberl (ORCID: https://orcid.org/0000-0002-4961-7832)
- Tsz Ching (ORCID: https://orcid.org/0000-0003-0001-9011)
- Elise E. Zhao (ORCID: https://orcid.org/0000-0003-3228-1399)
- M.-J. Kim (ORCID: https://orcid.org/0000-0001-8063-6911)
- Bo Dong (ORCID: https://orcid.org/0000-0001-7411-5052)
- Lyanne Chang
- Eric A. Bushong (ORCID: https://orcid.org/0000-0001-6195-2433)
- Dong Uk Yang (ORCID: https://orcid.org/0000-0003-0612-1439)
- Ken-Ching Chou
- Lisa Stowers (ORCID: https://orcid.org/0000-0002-4403-1269)
- Aram El Khoury (ORCID: https://orcid.org/0000-0003-1873-112X)
- Yuxuan Zhang (ORCID: https://orcid.org/0000-0003-4426-5636)
- Yuting Zhang (ORCID: https://orcid.org/0009-0004-2182-679X)
- Yongchuan Zhu
- Tam Quach
- Luca Patapoutian
- Elle McCue
- Keun-young Kim A (ORCID: https://orcid.org/0000-0002-4725-3211)
Institutions
- Scripps Research Institute (US)
- University of San Diego (US)
- University of California San Diego (US)
Publication Details
- Journal
- Science
- Published
- 2025-03-20
- DOI
- https://doi.org/10.1126/science.ado8316
- Citations
- 24
- Primary Topic
- Neuroscience and Neuropharmacology Research
- Type
- article
- Field-Weighted Citation Impact
- 21.82