A brain atlas of synapse protein lifetime across the mouse lifespan

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Bulovaite, Edita and Qiu, Zhen and Kratschke, Maximilian and Zgraj, Adrianna and Fricker, David G. and Tuck, Eleanor J. and Gokhale, Ragini and Koniaris, Babis and Jami, Shekib A. and Merino-Serrais, Paula and Husi, Elodie and Mendive-Tapia, Lorena and Vendrell, Marc and O’Dell, Thomas J. and DeFelipe, Javier and Komiyama, Noboru H. and Holtmaat, Anthony and Fransén, Erik and Grant, Seth G.N. (2022) A brain atlas of synapse protein lifetime across the mouse lifespan. Neuron, 110 (24). 4057-4073.e8. ISSN 0896-6273 (https://doi.org/10.1016/j.neuron.2022.09.009)

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Abstract

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.

ORCID iDs

Bulovaite, Edita, Qiu, Zhen ORCID logoORCID: https://orcid.org/0000-0002-0226-7855, Kratschke, Maximilian, Zgraj, Adrianna, Fricker, David G., Tuck, Eleanor J., Gokhale, Ragini, Koniaris, Babis, Jami, Shekib A., Merino-Serrais, Paula, Husi, Elodie, Mendive-Tapia, Lorena, Vendrell, Marc, O’Dell, Thomas J., DeFelipe, Javier, Komiyama, Noboru H., Holtmaat, Anthony, Fransén, Erik and Grant, Seth G.N.;
CORE (COnnecting REpositories)