title: Experience-dependent pruning of dendritic spines in visual cortex by tissue plasminogen activator.
abstract: Sensory experience physically rewires the brain in early postnatal life through unknown processes. Here, we identify a robust anatomical consequence of monocular deprivation (MD) in layer II/III of visual cortex that corresponds to the rapid, functional loss of responsiveness preceding any changes in axonal input. Protrusions on pyramidal cell apical dendrites increased steadily after eye opening, but were transiently lost through competitive mechanisms after brief MD only during the physiological critical period. Proteolysis by tissue-type plasminogen activator (tPA) conversely declined with age and increased with MD only in young mice. Targeted disruption of tPA release or its upstream regulation by glutamic acid decarboxylase (GAD65) prevented MD-induced spine loss that was pharmacologically rescued concomitant with critical period plasticity. An extracellular mechanism for structural remodeling that is limited to the binocular zone upon proper detection of competing inputs thus links early sensory experience to visual function.
authors.affiliation: Laboratory for Neuronal Circuit Development, Institute of Physical and Chemical Research (RIKEN), Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Nobuko
authors.initials: N
authors.lastname: Mataga
authors.forename: Yoko
authors.initials: Y
authors.lastname: Mizuguchi
authors.forename: Takao K
authors.initials: TK
authors.lastname: Hensch
mesh_terms: D000818:Animals; D049229:Dendritic Spines / Q000201:enzymology* / Q000502:physiology; D005968:Glutamate Decarboxylase / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D012683:Sensory Deprivation / Q000502:physiology*; D010959:Tissue Plasminogen Activator / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015349:Vision, Monocular / Q000502:physiology*; D014793:Visual Cortex / Q000166:cytology / Q000201:enzymology*
chemical_list: D007527:Isoenzymes; D010959:Tissue Plasminogen Activator; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2