Experience modifies the synaptome architecture in the developing and adult mouse brain

Synaptome architecture describes the spatiotemporal distribution of highly diverse excitatory synapses throughout the brain. Whether and how this architecture is impacted by experience and sensory input is unknown. We found that environmental enrichment and monocular visual deprivation drive large-scale reconfiguration of excitatory synapse populations in more than one hundred regions of the mouse brain. Different experiences modify distinct subsets of synapse types and subtypes, with patterns aligned with protein turnover rates and connectome architecture. Similarity in experience-dependent reconfiguration during development and adulthood indicates shared mechanisms of synaptome adaptation across the lifespan. Our findings support a population-selection model in which experiences drive adaptation by selectively modifying synapse types and subtypes distributed across the brain. Experience-driven reconfiguration of synaptome architecture shares features with the response to aging, sleep deprivation, brain injury and genetic mutations, supporting a unifying principle of brain adaptation.