title: Neuronal activity controls transsynaptic geometry.
abstract: The neuronal synapse is comprised of several distinct zones, including presynaptic vesicle zone (SVZ), active zone (AZ) and postsynaptic density (PSD). While correct relative positioning of these zones is believed to be essential for synaptic function, the mechanisms controlling their mutual localization remain unexplored. Here, we employ high-throughput quantitative confocal imaging, super-resolution and electron microscopy to visualize organization of synaptic subdomains in hippocampal neurons. Silencing of neuronal activity leads to reversible reorganization of the synaptic geometry, resulting in a increased overlap between immunostained AZ and PSD markers; in contrast, the SVZ-AZ spatial coupling is decreased. Bayesian blinking and bleaching (3B) reconstruction reveals that the distance between the AZ-PSD distance is decreased by 30 nm, while electron microscopy shows that the width of the synaptic cleft is decreased by 1.1 nm. Our findings show that multiple aspects of synaptic geometry are dynamically controlled by neuronal activity and suggest mutual repositioning of synaptic components as a potential novel mechanism contributing to the homeostatic forms of synaptic plasticity.
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London SE1 1UL, UK.|Department of Developmental Neurobiology, King's College London, London SE1 1UL, UK.
authors.forename: Oleg O
authors.initials: OO
authors.lastname: Glebov
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, London SE1 1UL, UK.
authors.forename: Susan
authors.initials: S
authors.lastname: Cox
authors.affiliation: Department of Developmental Neurobiology, King's College London, London SE1 1UL, UK.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Humphreys
authors.affiliation: Department of Developmental Neurobiology, King's College London, London SE1 1UL, UK.
authors.forename: Juan
authors.initials: J
authors.lastname: Burrone
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D006624:Hippocampus / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D051381:Rats; D013569:Synapses / Q000502:physiology / Q000648:ultrastructure*; D009435:Synaptic Transmission / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D061567:Voltage-Gated Sodium Channel Blockers / Q000494:pharmacology; D061566:Voltage-Gated Sodium Channels / Q000187:drug effects / Q000502:physiology
chemical_list: C113688:Bsn protein, rat; D009419:Nerve Tissue Proteins; D061567:Voltage-Gated Sodium Channel Blockers; D061566:Voltage-Gated Sodium Channels; D013779:Tetrodotoxin