Experiences are encoded by brainwide reprogramming of synaptome architecture

Woods, Hanan and Günar, Ülkü and Gillard, Sarah Catherine and Notman, Beverley and Yuan, Kunhao and Dominic, Digin and Robson, Emily and Varga, Gabor and Komiyama, Noboru H. and Qiu, Zhen and Sengpiel, Frank and Grant, Seth G.N. (2025) Experiences are encoded by brainwide reprogramming of synaptome architecture. Other. bioRxiv. (https://doi.org/10.64898/2025.12.12.693919)

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Abstract

Synaptome architecture describes the spatiotemporal distribution of highly diverse excitatory synapses throughout the brain. Whether and how this architecture is impacted by experience is key to understanding its role in learning and memory. We found that environmental enrichment and monocular visual deprivation drive large-scale, type-and subtype-specific reorganisation of excitatory synapses in more than one hundred brain regions. Each experience modifies distinct subsets of synapses, with patterns aligned with protein turnover rates and connectome architecture. These reorganisations occur during development and adulthood, revealing a conserved mechanism of synaptome plasticity across the lifespan. Our findings support a population-selection model in which experience drives adaptation by selectively modifying synapse varieties, generating a distributed trace of past experiences. Our results also point to synaptome architecture as a shared framework integrating experience, lifespan changes, sleep, genetic variation and disease.

ORCID iDs

Woods, Hanan, Günar, Ülkü, Gillard, Sarah Catherine, Notman, Beverley, Yuan, Kunhao, Dominic, Digin, Robson, Emily, Varga, Gabor, Komiyama, Noboru H., Qiu, Zhen ORCID logoORCID: https://orcid.org/0000-0002-0226-7855, Sengpiel, Frank and Grant, Seth G.N.;