Prolonged Period of Cortical Plasticity upon Redox Dysregulation in Fast-Spiking Interneurons.
Prolonged Period of Cortical Plasticity upon Redox Dysregulation in Fast-Spiking Interneurons.
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DOI：
10.1016/j.biopsych.2014.12.026
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发表时间：
2015-09-15
影响因子：
10.6
通讯作者：
Hensch TK
中科院分区：
文献类型：
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作者：
Morishita H;Cabungcal JH;Chen Y;Do KQ;Hensch TK
氧化应激和体细胞周围GABA回路的特异性损伤是精神分裂症脑及其动物模型的标志。这些快速刺激的抑制性中间神经元的适当成熟通常定义了经验依赖的皮层可塑性的关键时期。在这里，我们通过基因诱导氧化还原失调将这些过程联系起来，这些氧化还原失调仅限于这些细小蛋白阳性细胞，并以视觉系统为模型（3 - 6只小鼠/组）研究了对关键期可塑性的影响。氧化应激伴随着神经周围网络的显著丧失，神经周围网络通常包裹着成熟的快速尖峰细胞，以限制成年细胞的可塑性。因此，即使在其自然关键期的高峰之后，新皮层仍保持可塑性。当氧化还原失调以兴奋性主细胞为目标时，这些效应未被观察到。因此，细胞特异性的氧化还原状态调节平衡了皮质网络的可塑性和稳定性。大脑可塑性的非正常发育轨迹可能在一定程度上是精神疾病病理生理学的基础。这种长期的发育可塑性可能反过来为针对精神分裂症大脑可塑性的认知干预提供治疗机会。
Oxidative stress and the specific impairment of peri-somatic GABA 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. Here, we link 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 (3–6mice/group). 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. A cell-specific regulation of redox state thus balances plasticity and stability of cortical networks. Mis-timed 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.