@article{8d617031be7748a9bbf70ed40b11df94,
title = "Multi-synaptic boutons are a feature of CA1 hippocampal connections in the stratum oriens",
abstract = "Excitatory synapses are typically described as single synaptic boutons (SSBs), where one presynaptic bouton contacts a single postsynaptic spine. Using serial section block-face scanning electron microscopy, we found that this textbook definition of the synapse does not fully apply to the CA1 region of the hippocampus. Roughly half of all excitatory synapses in the stratum oriens involved multi-synaptic boutons (MSBs), where a single presynaptic bouton containing multiple active zones contacted many postsynaptic spines (from 2 to 7) on the basal dendrites of different cells. The fraction of MSBs increased during development (from postnatal day 22 [P22] to P100) and decreased with distance from the soma. Curiously, synaptic properties such as active zone (AZ) or postsynaptic density (PSD) size exhibited less within-MSB variation when compared with neighboring SSBs, features that were confirmed by super-resolution light microscopy. Computer simulations suggest that these properties favor synchronous activity in CA1 networks.",
keywords = "axon, connectome, CP: Neuroscience, dendrite, hippocampus, multi-synaptic bouton, network synchrony, synapse",
author = "Mark Rigby and Grillo, {Federico W.} and Benjamin Compans and Guilherme Neves and Julia Gallinaro and Sophie Nashashibi and Sally Horton and {Pereira Machado}, {Pedro M.} and Carbajal, {Maria Alejandra} and Gema Vizcay-Barrena and Florian Levet and Sibarita, {Jean Baptiste} and Angus Kirkland and Fleck, {Roland A.} and Claudia Clopath and Juan Burrone",
note = "Funding Information: We would like to thank Winnie Wefelmeyer for useful feedback and comments on the manuscript and Vincenzo Mastrolia for the graphical abstract. We would also like to thank Nicolas Bourg and Abbelight for the SAFeRedSTORM module and software, as well as Olympus for the IX3 microscope used for dSTORM. This research was funded in whole, or in part, by the Wellcome Trust (095589/Z/11/Z and 215508/Z/19/Z to J.B. 200790/Z/16/Z to C.C. and an equipment grant 108461/Z/15/Z to R.A.F. and J.B.). For the purpose of open access, the author has applied a CC BY public copyright license to any author-accepted manuscript version arising from this submission. This project has received funding from the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement no. 894933 to B.C. This work was also supported by a BBSRC project grant (BB/N013956/1) to C.C.; a Simons Foundation grant (564408) to C.C.; an EPSRC grant (EP/R035806/1) to C.C.; an ERC Starter Grant (282047) to J.B.; a BBSRC project grant (BB/S000526/1) to J.B.; a Royal Society Industry Fellowship (INF∖R2∖202061) to R.A.F.; a national infrastructure France BioImaging (ANR-10-INBS-04-01) to J.-B.S. and F.L.; and an NC3Rs Training Fellowship to M.R. S.H. was funded by an MRC-Sackler PhD studentship. Finally, we acknowledge the support of the Rosalind Franklin Institute. M.R. F.G. B.C. G.N. and J.B. conceived and designed the experiments. M.R. F.G. G.N. S.H. and S.N. segmented and analyzed the SBFSEM datasets. P.M.P.M. M.A.C. G.V.-B. A.K. and R.A.F. provided technical expertise and guidance on EM techniques. P.M.P.M. M.A.C. and G.V.-B. processed the samples for SBFSEM and acquired the images. B.C. carried out the STORM imaging and the data analysis. F.L. and J.-B.S. developed the STORM analysis software and assisted B.C. with 3D data analysis. J.G. and C.C. carried out the mathematical modeling. M.R. B.C. G.N. J.G. C.C. and J.B. wrote the paper with feedback from authors. The authors declare no competing interests. Funding Information: We would like to thank Winnie Wefelmeyer for useful feedback and comments on the manuscript and Vincenzo Mastrolia for the graphical abstract. We would also like to thank Nicolas Bourg and Abbelight for the SAFeRedSTORM module and software, as well as Olympus for the IX3 microscope used for dSTORM. This research was funded in whole, or in part, by the Wellcome Trust ( 095589/Z/11/Z and 215508/Z/19/Z to J.B., 200790/Z/16/Z to C.C., and an equipment grant 108461/Z/15/Z to R.A.F. and J.B.). For the purpose of open access, the author has applied a CC BY public copyright license to any author-accepted manuscript version arising from this submission. This project has received funding from the European Union{\textquoteright}s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement no. 894933 to B.C. This work was also supported by a BBSRC project grant ( BB/N013956/1 ) to C.C.; a Simons Foundation grant ( 564408 ) to C.C.; an EPSRC grant ( EP/R035806/1 ) to C.C.; an ERC Starter Grant ( 282047 ) to J.B.; a BBSRC project grant ( BB/S000526/1 ) to J.B.; a Royal Society Industry Fellowship ( INF∖R2∖202061 ) to R.A.F.; a national infrastructure France BioImaging ( ANR-10-INBS-04-01 ) to J.-B.S. and F.L.; and an NC3Rs Training Fellowship to M.R. S.H. was funded by an MRC -Sackler PhD studentship. Finally, we acknowledge the support of the Rosalind Franklin Institute . Publisher Copyright: {\textcopyright} 2023 The Author(s)",
year = "2023",
month = may,
day = "30",
doi = "10.1016/j.celrep.2023.112397",
language = "English",
volume = "42",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Elsevier BV",
number = "5",
}