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A brain atlas of synapse protein lifetime across the mouse lifespan

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Bulovaite, Edita, Qiu, Zhen, Kratschke, Maximilian, Zgraj, Adrianna, Fricker, David G., Tuck, Eleanor J., Gokhale, Ragini, Koniaris, Babis +11 more·2022·Neuron
DOI 10.1016/j.neuron.2022.09.009PMC PMC9789179

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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.

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  • The lifetimes of brain proteins vary widely.

    “Moreover, the lifetimes of brain proteins vary widely [22][23][24]”

    From A feature and not a bug: Replication failures can lead to new biology (2026) · cites this paper as [22]

    The Abstract reports that PSD95 lifetimes at excitatory synapses across the mouse brain range from hours to several months. This supports wide variation in the lifetime of one brain protein across synapses, but does not establish that lifetimes vary widely among brain proteins generally. (LLM, conf=0.85)

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Cited by

Sorted by citations

Authors
Bulovaite, E., Qiu, Z., Kratschke, M., Zgraj, A., Fricker, D. G., Tuck, E. J., Gokhale, R., Koniaris, B., Jami, S. A., Merino-Serrais, P., Husi, E., Mendive-Tapia, L., Vendrell, M., O’Dell, T. J., DeFelipe, J., Komiyama, N. H., Holtmaat, A., Fransén, E., & Grant, S. G. N.
Affiliations
  • University of Edinburgh (GB)
  • Edinburgh Napier University (GB)
  • University of California, Los Angeles (US)
  • University of Geneva (CH)
  • Centre for Inflammation Research (GB)
  • Consejo Superior de Investigaciones Científicas (ES)
  • Simons Initiative for the Developing Brain (GB)
  • Science for Life Laboratory (SE)
Corresponding author
Grant, Seth G.N.
ORCID
Venue
Neuron
Publisher
Elsevier BV
Published
2022-12
Volume
110
Issue
24
Pages
4057-4073.e8
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2022.09.009
PMC
PMC9789179
OpenAlex
W4302008264
Cited by
111
References
11
Citations by year
2026: 35 · 2025: 30 · 2024: 26 · 2023: 15 · 2022: 5
FWCI
8.44
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuron (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Discovery Research Portal (University of Dundee) (publishedVersion, cc-by)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (acceptedVersion, cc-by)
  • PubMed Central (acceptedVersion)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by)
  • Edinburgh Napier Research Repository (Edinburgh Napier University) (submittedVersion, cc-by)
Funders
  • National Science Foundation
  • Wellcome Trust (529085, 202932, 695568)
  • European Commission (202932, 695568, HORIZON2020, 529085)
  • International Foundation for Research in Paraplegia
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (51NF40, 185897, 27658, 173125)
  • National Institute of Mental Health (R01MH060919)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
PSD-95, postsynaptic density, excitatory synapses, mouse brain atlas, lifespan, brain aging, brain development, autism spectrum disorder, schizophrenia, memory storage, innate behavior
MeSH terms
Disks Large Homolog 4 Protein, Animals, Brain, Longevity, Neurons, Synapses, Mice

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