在精神分裂症小鼠模型中恢复成年期类似野生型的 CA1 网络动力学和行为。
Restoring wild-type-like CA1 network dynamics and behavior during adulthood in a mouse model of schizophrenia.
机构信息
Department of Basic Neuroscience, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Institut de Neurobiologie de la Méditerranée, UMR 1249 INSERM, Marseille, France.
出版信息
Nat Neurosci. 2018 Oct;21(10):1412-1420. doi: 10.1038/s41593-018-0225-y. Epub 2018 Sep 17.
Abstract
Schizophrenia is a severely debilitating neurodevelopmental disorder. Establishing a causal link between circuit dysfunction and particular behavioral traits that are relevant to schizophrenia is crucial to shed new light on the mechanisms underlying the pathology. We studied an animal model of the human 22q11 deletion syndrome, the mutation that represents the highest genetic risk of developing schizophrenia. We observed a desynchronization of hippocampal neuronal assemblies that resulted from parvalbumin interneuron hypoexcitability. Rescuing parvalbumin interneuron excitability with pharmacological or chemogenetic approaches was sufficient to restore wild-type-like CA1 network dynamics and hippocampal-dependent behavior during adulthood. In conclusion, our data provide insights into the network dysfunction underlying schizophrenia and highlight the use of reverse engineering to restore physiological and behavioral phenotypes in an animal model of neurodevelopmental disorder.
摘要
精神分裂症是一种严重使人虚弱的神经发育障碍。在电路功能障碍和与精神分裂症相关的特定行为特征之间建立因果关系，对于揭示潜在病理机制的新途径至关重要。我们研究了人类 22q11 缺失综合征的动物模型，该突变代表了发展精神分裂症的最高遗传风险。我们观察到海马神经元集合的去同步化，这是由于 Parvalbumin 中间神经元兴奋性降低所致。用药理学或化学遗传学方法恢复 Parvalbumin 中间神经元的兴奋性足以恢复成年期类似野生型的 CA1 网络动力学和海马依赖性行为。总之，我们的数据提供了对精神分裂症相关网络功能障碍的深入了解，并强调了使用逆向工程在神经发育障碍的动物模型中恢复生理和行为表型的重要性。
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