Journal
BIOLOGICAL PSYCHIATRY
Volume 78, Issue 6, Pages 396-402Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2014.12.026
Keywords
GABA; Oxidative stress; Parvalbumin; Perineuronal net; Schizophrenia; Visual cortex
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Funding
- National Institutes of Health [1DP1OD003699, 1P50MH094271]
- Swiss National Science Foundation [31-116689]
- National Center of Competence in Research SYNAPSY - The Synaptic Bases of Mental Diseases - Swiss National Science Foundation [51AU40_125759]
- Fondation Damm-Etienne
- Brain & Behavior Research Foundation
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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.
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