Sleep maintains excitatory synapse diversity in the cortex and hippocampus
Dimitra Koukaroudi, Zhen Qiu, Erik Fransén, Ragini Gokhale, Edita Bulovaite, Noboru H. Komiyama, Julie Seibt, Seth G. N. Grant
Abstract
Insufficient sleep is a global problem with serious consequences for cognition and mental health.1Chattu V.K. Manzar M.D. Kumary S. Burman D. Spence D.W. Pandi-Perumal S.R. The Global Problem of Insufficient Sleep and Its Serious Public Health Implications.Healthcare (Basel). 2018; 71PubMed Google Scholar Synapses play a central role in many aspects of cognition, including the crucial function of memory consolidation during sleep.2Brodt S. Inostroza M. Niethard N. Born J. Sleep—A brain-state serving systems memory consolidation.Neuron. 2023; 111: 1050-1075Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar Interference with the normal expression or function of synapse proteins is a cause of cognitive, mood, and other behavioral problems in over 130 brain disorders.3Bayes A. van de Lagemaat L.N. Collins M.O. Croning M.D. Whittle I.R. Choudhary J.S. Grant S.G. Characterization of the proteome, diseases and evolution of the human postsynaptic density.Nat. Neurosci. 2011; 14: 19-21Crossref PubMed Scopus (353) Google Scholar Sleep deprivation (SD) has also been reported to alter synapse protein composition and synapse number, although with conflicting results.4Cirelli C. Tononi G. Effects of sleep and waking on the synaptic ultrastructure.Philos. Trans. R. Soc. Lond. B Biol. Sci. 2020; 37520190235Crossref PubMed Scopus (23) Google Scholar,5Havekes R. Aton S.J. Impacts of Sleep Loss versus Waking Experience on Brain Plasticity: Parallel or Orthogonal?.Trends Neurosci. 2020; 43: 385-393Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar,6Puentes-Mestril C. Aton S.J. Linking Network Activity to Synaptic Plasticity during Sleep: Hypotheses and Recent Data.Front. Neural Circuits. 2017; 11: 61Crossref PubMed Scopus (85) Google Scholar,7Raven F. Van der Zee E.A. Meerlo P. Havekes R. The role of sleep in regulating structural plasticity and synaptic strength: implications for memory and cognitive function.Sleep Med. Rev. 2018; 39: 3-11Crossref PubMed Scopus (196) Google Scholar In our study, we conducted synaptome mapping of excitatory synapses in 125 regions of the mouse brain and found that sleep deprivation selectively reduces synapse diversity in the cortex and in the CA1 region of the hippocampus. Sleep deprivation targeted specific types and subtypes of excitatory synapses while maintaining total synapse density (synapse number/area). Synapse subtypes with longer protein lifetimes exhibited resilience to sleep deprivation, similar to observations in aging and genetic perturbations. Moreover, the altered synaptome architecture affected the responses to neural oscillations, suggesting that sleep plays a vital role in preserving cognitive function by maintaining the brain's synaptome architecture.