Altered excitatory-inhibitory balance in the NMDA-hypofunction model of schizophrenia
Altered excitatory-inhibitory balance in the NMDA-hypofunction model of schizophrenia
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DOI：
10.3389/neuro.02/006.2008
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发表时间：
2008-01-01
影响因子：
4.8
通讯作者：
Gloveli, Tengis
中科院分区：
文献类型：
--
作者：
Kehrer, Colin;Maziashvili, Nino;Gloveli, Tengis
精神分裂症是一种常见的精神疾病，发病率很高，约占世界人口的1%。精神分裂症的基本神经递质病理学仍然很难定义，尽管在过去的半个世纪里，在确定疾病的神经化学和病理学异常方面取得了巨大进展。多巴胺/5-羟色胺假说最初为精神分裂症的神经化学研究提供了动力。然而，近年来，注意力已经转移到谷氨酸系统，在中枢神经系统中的主要兴奋性神经递质和精神分裂症的各个脑区在网络水平上的兴奋性和抑制性传递之间的功能失衡的概念。表明NMDA受体亚型在精神分裂症病因学中的中心作用的证据导致了这种疾病的NMDA功能低下模型和使用苯环己哌啶作为在动物模型中诱导NMDA功能低下状态的手段。本综述的目的是讨论最近的研究结果突出的重要性，NMDA功能减退模型的精神分裂症，无论是从临床的角度来看，以及在打开一条线的研究，使电生理研究在细胞和网络水平在体外。特别是，兴奋抑制（E/I）平衡的NMDA功能减退模型的疾病和由此产生的网络行为的变化，特别是在γ频率振荡活动的变化，将进行讨论。
Schizophrenia is a common psychiatric disorder of high incidence, affecting approximately 1% of the world population. The essential neurotransmitter pathology of schizophrenia remains poorly defined, despite huge advances over the past half-century in identifying neurochemical and pathological abnormalities in the disease. The dopamine/serotonin hypothesis has originally provided much of the momentum for neurochemical research in schizophrenia. In recent years, the attention has, however, shifted to the glutamate system, the major excitatory neurotransmitter in the CNS and towards a concept of functional imbalance between excitatory and inhibitory transmission at the network level in various brain regions in schizophrenia. The evidence indicating a central role for the NMDA-receptor subtype in the aetiology of schizophrenia has led to the NMDA-hypofunction model of this disease and the use of phencyclidines as a means to induce the NMDA-hypofunction state in animal models. The purpose of this review is to discuss recent findings highlighting the importance of the NMDA-hypofunction model of schizophrenia, both from a clinical perspective, as well as in opening a line of research, which enables electrophysiological studies at the cellular and network level in vitro. In particular, changes in excitation-inhibition (E/I) balance in the NMDA-hypofunction model of the disease and the resulting changes in network behaviours, particularly in gamma frequency oscillatory activity, will be discussed.