title: Prolonged Period of Cortical Plasticity upon Redox Dysregulation in Fast-Spiking Interneurons.
abstract: BACKGROUND
  Oxidative stress and the specific impairment of perisomatic gamma-aminobutyric acid circuits are hallmarks of the schizophrenic brain and its animal models. Proper maturation of these fast-spiking inhibitory interneurons normally defines critical periods of experience-dependent cortical plasticity.
  
  
  METHODS
  Here, we linked these processes by genetically inducing a redox dysregulation restricted to such parvalbumin-positive cells and examined the impact on critical period plasticity using the visual system as a model (3-6 mice/group).
  
  
  RESULTS
  Oxidative stress was accompanied by a significant loss of perineuronal nets, which normally enwrap mature fast-spiking cells to limit adult plasticity. Accordingly, the neocortex remained plastic even beyond the peak of its natural critical period. These effects were not seen when redox dysregulation was targeted in excitatory principal cells.
  
  
  CONCLUSIONS
  A cell-specific regulation of redox state thus balances plasticity and stability of cortical networks. Mistimed developmental trajectories of brain plasticity may underlie, in part, the pathophysiology of mental illness. Such prolonged developmental plasticity may, in turn, offer a therapeutic opportunity for cognitive interventions targeting brain plasticity in schizophrenia.
authors.affiliation: FM Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Morishita
authors.affiliation: Department of Psychiatry, Center for Psychiatric Neuroscience, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
authors.forename: Jan-Harry
authors.initials: JH
authors.lastname: Cabungcal
authors.affiliation: School of Pharmacy, University of Colorado at Denver, Boulder, Colorado.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Psychiatry, Center for Psychiatric Neuroscience, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
authors.forename: Kim Q
authors.initials: KQ
authors.lastname: Do
authors.affiliation: FM Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; Center for Brain Science, Department of Molecular Cellular Biology, Harvard University, Cambridge, Massachusetts.. Electronic address: hensch@mcb.harvard.edu.
authors.forename: Takao K
authors.initials: TK
authors.lastname: Hensch
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D005109:Extracellular Matrix / Q000378:metabolism; D059330:GABAergic Neurons / Q000378:metabolism / Q000502:physiology*; D005721:Glutamate-Cysteine Ligase / Q000235:genetics; D007395:Interneurons / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism; D009473:Neuronal Plasticity; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010320:Parvalbumins; D012683:Sensory Deprivation / Q000502:physiology; D014793:Visual Cortex / Q000378:metabolism / Q000502:physiology*
chemical_list: D010320:Parvalbumins; D005721:Glutamate-Cysteine Ligase
keywords: GABA; Oxidative stress; Parvalbumin; Perineuronal net; Schizophrenia; Visual cortex