title: Permissive proteolytic activity for visual cortical plasticity.
abstract: The serine protease, tissue-type plasminogen activator (tPA) is a key regulator of extracellular proteolytic cascades. We demonstrate a requirement for tPA signaling in the experience-dependent plasticity of mouse visual cortex during the developmental critical period. Proteolytic activity by tPA in the binocular zone was typically increased within 2 days of monocular deprivation (MD). This regulation failed to occur in glutamic acid decarboxylase (GAD) 65 knockout mice, an animal model of impaired ocular dominance plasticity because of reduced gamma-aminobutyric acid (GABA)-mediated transmission described previously. Loss of responsiveness to the deprived eye consequent to MD was conversely suppressed in mice lacking tPA despite normal levels of neuronal activity. Plasticity was restored in a gene dose-dependent manner, or by direct tPA infusion. Permissive amounts of tPA may, thus, couple functional to structural changes downstream of the excitatory-inhibitory balance that triggers visual cortical plasticity. Our results not only support a molecular cascade leading to neurite outgrowth after sensory deprivation, but also identify a valuable tool for further proteomic and genomic dissection of experience-dependent plasticity downstream of electrical activity.
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: Nobuo
authors.initials: N
authors.lastname: Nagai
authors.forename: Takao K
authors.initials: TK
authors.lastname: Hensch
mesh_terms: D000818:Animals; D010450:Endopeptidases / Q000378:metabolism*; D005968:Glutamate Decarboxylase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008959:Models, Neurological; D016501:Neurites / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology; D010959:Tissue Plasminogen Activator / Q000494:pharmacology; D015349:Vision, Monocular / Q000502:physiology; D014793:Visual Cortex / Q000187:drug effects / Q000502:physiology*; D014795:Visual Pathways / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D007527:Isoenzymes; D005680:gamma-Aminobutyric Acid; D010450:Endopeptidases; D010959:Tissue Plasminogen Activator; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2