Prolonged Period of Cortical Plasticity upon Redox Dysregulation in Fast-Spiking Interneurons

Biol Psychiatry. 2015 Sep 15;78(6):396-402. doi: 10.1016/j.biopsych.2014.12.026. Epub 2015 Jan 24.


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.

Keywords: GABA; Oxidative stress; Parvalbumin; Perineuronal net; Schizophrenia; Visual cortex.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological
  • Animals
  • Extracellular Matrix / metabolism
  • GABAergic Neurons / metabolism
  • GABAergic Neurons / physiology*
  • Glutamate-Cysteine Ligase / genetics
  • Interneurons / metabolism*
  • Mice, Inbred C57BL
  • Microglia / metabolism
  • Neuronal Plasticity*
  • Oxidation-Reduction
  • Oxidative Stress*
  • Parvalbumins
  • Sensory Deprivation / physiology
  • Visual Cortex / metabolism
  • Visual Cortex / physiology*


  • Parvalbumins
  • Glutamate-Cysteine Ligase