A brain atlas of synapse protein lifetime across the mouse lifespan

Edita Bulovaite, Zhen Qiu, Maximilian Kratschke, Adrianna Zgraj, David G Fricker, Eleanor J Tuck, Ragini Gokhale, Babis Koniaris, Shekib A Jami, Paula Merino-Serrais, Elodie Husi, Lorena Mendive-Tapia, Marc Vendrell, Thomas J O'Dell, Javier DeFelipe, Noboru H Komiyama, Anthony Holtmaat, Erik Fransén, Seth G N Grant

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

The lifetime of proteins in synapses is important for their signaling, maintenance, and remodeling, and for memory duration. We quantified the lifetime of endogenous PSD95, an abundant postsynaptic protein in excitatory synapses, at single-synapse resolution across the mouse brain and lifespan, generating the Protein Lifetime Synaptome Atlas. Excitatory synapses have a wide range of PSD95 lifetimes extending from hours to several months, with distinct spatial distributions in dendrites, neurons, and brain regions. Synapses with short protein lifetimes are enriched in young animals and in brain regions controlling innate behaviors, whereas synapses with long protein lifetimes accumulate during development, are enriched in the cortex and CA1 where memories are stored, and are preferentially preserved in old age. Synapse protein lifetime increases throughout the brain in a mouse model of autism and schizophrenia. Protein lifetime adds a further layer to synapse diversity and enriches prevailing concepts in brain development, aging, and disease.

Original languageEnglish
Publication statusPublished - 5 Oct 2022


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