title: Spontaneous Activity Drives Local Synaptic Plasticity In Vivo.
abstract: Spontaneous activity fine-tunes neuronal connections in the developing brain. To explore the underlying synaptic plasticity mechanisms, we monitored naturally occurring changes in spontaneous activity at individual synapses with whole-cell patch-clamp recordings and simultaneous calcium imaging in the mouse visual cortex in vivo. Analyzing activity changes across large populations of synapses revealed a simple and efficient local plasticity rule: synapses that exhibit low synchronicity with nearby neighbors (<12 μm) become depressed in their transmission frequency. Asynchronous electrical stimulation of individual synapses in hippocampal slices showed that this is due to a decrease in synaptic transmission efficiency. Accordingly, experimentally increasing local synchronicity, by stimulating synapses in response to spontaneous activity at neighboring synapses, stabilized synaptic transmission. Finally, blockade of the high-affinity proBDNF receptor p75(NTR) prevented the depression of asynchronously stimulated synapses. Thus, spontaneous activity drives local synaptic plasticity at individual synapses in an "out-of-sync, lose-your-link" fashion through proBDNF/p75(NTR) signaling to refine neuronal connectivity. VIDEO ABSTRACT.
authors.affiliation: Department of Synapse and Network Development, Netherlands Institute for Neuroscience, 1105 BA Amsterdam, The Netherlands.
authors.forename: Johan
authors.initials: J
authors.lastname: Winnubst
authors.affiliation: Department of Synapse and Network Development, Netherlands Institute for Neuroscience, 1105 BA Amsterdam, The Netherlands.
authors.forename: Juliette E
authors.initials: JE
authors.lastname: Cheyne
authors.affiliation: Department of Synapse and Network Development, Netherlands Institute for Neuroscience, 1105 BA Amsterdam, The Netherlands.
authors.forename: Dragos
authors.initials: D
authors.lastname: Niculescu
authors.affiliation: Department of Synapse and Network Development, Netherlands Institute for Neuroscience, 1105 BA Amsterdam, The Netherlands. Electronic address: c.lohmann@nin.knaw.nl.
authors.forename: Christian
authors.initials: C
authors.lastname: Lohmann
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D003198:Computer Simulation; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D009415:Nerve Net / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D011810:Quinoxalines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014793:Visual Cortex / Q000166:cytology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D008164:Luminescent Proteins; D011810:Quinoxalines; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D002118:Calcium