Synaptic architecture of a memory engram in the mouse hippocampus. 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, and Anton Maximov. Science 387, eado8316 (2025). https://doi.org/10.1126/science.ado8316
electron microscopy, chemogenetic tagging
Mouse hippocampus

The authors studied how long-term structural changes establish fear memories on the Schaffer collateral synapses using a combination of 3D electron microscopy, chemogenetic tagging and behavioral analysis. Their results suggest that formation of long-term engrams is associated with a selective presynaptically driven increase in the number and size of multisynaptic boutons, even without the involvement of simultaneous activation of synaptically connected neurons.
“Our findings highlight a mechanism by which projection neurons involved in memory acquisition increase their wiring complexity while maintaining the steady-state arrangements of individual synaptic sites.”