Despite multiple lines of research, a mechanistic understanding of schizophrenia remains elusive. Neuroimaging studies have yielded observations that can be used in translational studies in animals to attempt to uncover their cellular and circuit basis and their significance for the diseased human brain. Enhanced D2 stimulation in the striatum is a well replicated and established observation in patients with schizophrenia. This "bedside" observation was reproduced "at the bench" level by creating a transgenic mouse overexpressing D2 receptors in dorsal striatum (D2R-OE mouse). The D2R-OE mouse showed multiple behavioral, molecular, electrophysiological and anatomical alterations. Some of these are consistent with findings in patients with schizophrenia, providing construct validity to the model and mechanistic insights for the observations made in humans. Other findings were novel, and provide an opportunity for a reverse translational effort back into the clinic. In this review we will summarize the process of translation and back translation from the D2R-OE mouse and describe the insights into the pathophysiology of the disease gained through this type of translational work.

中文翻译：

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从“床边”到“长凳”再到背部：研究精神分裂症中多巴胺功能障碍的一种转化方法。

尽管有多方面的研究，对精神分裂症的机械理解仍然难以捉摸。神经影像学研究已经产生了可用于动物转化研究的观察结果，以试图揭示它们的细胞和电路基础以及它们对患病的人脑的重要性。在精神分裂症患者中，纹状体中D2刺激的增强得到了很好的复制和确定的观察。通过在背侧纹状体中产生过表达D2受体的转基因小鼠（D2R-OE小鼠），可以在“替补席”水平上复制“卧床”观察结果。D2R-OE小鼠表现出多种行为，分子，电生理和解剖学改变。其中一些与精神分裂症患者的发现相符，为模型提供构造效度，并为人类观察提供机械学见解。其他发现是新颖的，并为反向翻译工作回到临床提供了机会。在这篇综述中，我们将总结从D2R-OE小鼠进行翻译和反向翻译的过程，并描述通过这种类型的翻译工作获得的对该疾病的病理生理学的见解。