title: Progressive maturation of silent synapses governs the duration of a critical period.
abstract: During critical periods, all cortical neural circuits are refined to optimize their functional properties. The prevailing notion is that the balance between excitation and inhibition determines the onset and closure of critical periods. In contrast, we show that maturation of silent glutamatergic synapses onto principal neurons was sufficient to govern the duration of the critical period for ocular dominance plasticity in the visual cortex of mice. Specifically, postsynaptic density protein-95 (PSD-95) was absolutely required for experience-dependent maturation of silent synapses, and its absence before the onset of critical periods resulted in lifelong juvenile ocular dominance plasticity. Loss of PSD-95 in the visual cortex after the closure of the critical period reinstated silent synapses, resulting in reopening of juvenile-like ocular dominance plasticity. Additionally, silent synapse-based ocular dominance plasticity was largely independent of the inhibitory tone, whose developmental maturation was independent of PSD-95. Moreover, glutamatergic synaptic transmission onto parvalbumin-positive interneurons was unaltered in PSD-95 KO mice. These findings reveal not only that PSD-95-dependent silent synapse maturation in visual cortical principal neurons terminates the critical period for ocular dominance plasticity but also indicate that, in general, once silent synapses are consolidated in any neural circuit, initial experience-dependent functional optimization and critical periods end.
authors.affiliation: Molecular Neurobiology, European Neuroscience Institute, D-37077 Göttingen, Germany; Göttingen Graduate School for Neurosciences and Molecular Biosciences, D-37077 Göttingen, Germany;
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Huang
authors.affiliation: Göttingen Graduate School for Neurosciences and Molecular Biosciences, D-37077 Göttingen, Germany; Bernstein Fokus Neurotechnologie and Department of Systems Neuroscience, Johann-Friedrich-Blumenbach Institut für Zoologie und Anthropologie, Universität Göttingen, D-37075 Göttingen, Germany;
authors.forename: Sophia K
authors.initials: SK
authors.lastname: Stodieck
authors.affiliation: Bernstein Fokus Neurotechnologie and Department of Systems Neuroscience, Johann-Friedrich-Blumenbach Institut für Zoologie und Anthropologie, Universität Göttingen, D-37075 Göttingen, Germany;
authors.forename: Bianka
authors.initials: B
authors.lastname: Goetze
authors.affiliation: Molecular Neurobiology, European Neuroscience Institute, D-37077 Göttingen, Germany; Göttingen Graduate School for Neurosciences and Molecular Biosciences, D-37077 Göttingen, Germany;
authors.forename: Lei
authors.initials: L
authors.lastname: Cui
authors.affiliation: Molecular Neurobiology, European Neuroscience Institute, D-37077 Göttingen, Germany; Göttingen Graduate School for Neurosciences and Molecular Biosciences, D-37077 Göttingen, Germany;
authors.forename: Man Ho
authors.initials: MH
authors.lastname: Wong
authors.affiliation: Bernstein Fokus Neurotechnologie and Department of Systems Neuroscience, Johann-Friedrich-Blumenbach Institut für Zoologie und Anthropologie, Universität Göttingen, D-37075 Göttingen, Germany;
authors.forename: Colin
authors.initials: C
authors.lastname: Wenzel
authors.affiliation: Bernstein Fokus Neurotechnologie and Department of Systems Neuroscience, Johann-Friedrich-Blumenbach Institut für Zoologie und Anthropologie, Universität Göttingen, D-37075 Göttingen, Germany;
authors.forename: Leon
authors.initials: L
authors.lastname: Hosang
authors.affiliation: Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260;
authors.forename: Yan
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Bernstein Fokus Neurotechnologie and Department of Systems Neuroscience, Johann-Friedrich-Blumenbach Institut für Zoologie und Anthropologie, Universität Göttingen, D-37075 Göttingen, Germany; Sensory Collaborative Research Center 889, University of Göttingen, D-37075 Göttingen, Germany sloewel@gwdg.de oschlue@gwdg.de.
authors.forename: Siegrid
authors.initials: S
authors.lastname: Löwel
authors.affiliation: Molecular Neurobiology, European Neuroscience Institute, D-37077 Göttingen, Germany; Sensory Collaborative Research Center 889, University of Göttingen, D-37075 Göttingen, Germany sloewel@gwdg.de oschlue@gwdg.de.
authors.forename: Oliver M
authors.initials: OM
authors.lastname: Schlüter
mesh_terms: D000818:Animals; D001931:Brain Mapping; D000076122:Disks Large Homolog 4 Protein; D023882:Dominance, Ocular / Q000502:physiology; D005260:Female; D005973:Glutamine / Q000502:physiology; D051528:Guanylate Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009415:Nerve Net / Q000254:growth & development* / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D018091:Receptors, AMPA / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D014793:Visual Cortex / Q000254:growth & development* / Q000502:physiology*
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D008565:Membrane Proteins; D018091:Receptors, AMPA; D005973:Glutamine; D051528:Guanylate Kinases
keywords: PSD-95; critical period; ocular dominance plasticity; silent synapse; visual cortex