Accumulating evidence supports parvalbumin expressing inhibitory interneuron (PV IN) dysfunction in the prefrontal cortex as a cause for cognitive impairment associated with schizophrenia (CIAS). PV IN decreased activity is suggested to be the culprit for many of the EEG deficits measured in patients, which correlate with deficits in working memory (WM), cognitive flexibility and attention. In the last few decades, CIAS has been recognized as a heavy burden on the quality of life of patients with schizophrenia, but little progress has been made in finding new treatment options. An important limiting factor in this process is the lack of adequate preclinical models and an incomplete understanding of the circuits engaged in cognition. In this study, we back-translated an auditory stimulation protocol regularly used in human EEG studies into mice and combined it with optogenetics to investigate the role of prefrontal cortex PV INs in excitatory/inhibitory balance and cortical processing. We also assessed spatial WM and reversal learning (RL) during inhibition of prefrontal cortex PV INs. We found significant impairments in trial-to-trial reliability, increased basal network activity and increased oscillation power at 20–60 Hz, and a decreased signal-to-noise ratio, but no significant impairments in behavior. These changes reflect some but not all neurophysiological deficits seen in patients with schizophrenia, suggesting that other neuronal populations and possibly brain regions are involved as well. Our work supports and expands previous findings and highlights the versatility of an approach that combines innovative technologies with back-translated tools used in humans.

中文翻译：

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前额叶皮层中小白蛋白中间神经元活性的抑制概括了精神分裂症的兴奋/抑制平衡和感觉加工受损的特征。

越来越多的证据支持前额叶皮层中表达抑制白蛋白的抑制性中间神经元（PV IN）功能障碍，这是与精神分裂症（CIAS）相关的认知障碍的原因。PV IN活性下降被认为是患者测量的许多EEG缺陷的元凶，这与工作记忆（WM），认知灵活性和注意力的缺陷有关。在过去的几十年中，CIAS被认为是精神分裂症患者生活质量的沉重负担，但是在寻找新的治疗选择方面进展甚微。这个过程中的一个重要限制因素是缺乏足够的临床前模型以及对参与认知的回路的不完全理解。在这个研究中，我们将在人类脑电图研究中经常使用的听觉刺激方案回译为小鼠，并将其与光遗传学相结合，以研究前额叶皮层PV IN在兴奋性/抑制性平衡和皮层加工中的作用。我们还评估了前额叶皮层PV INs抑制过程中的空间WM和逆向学习（RL）。我们发现试验至试验的可靠性受到明显损害，基础网络活动增加，在20–60 Hz时振荡功率增加，信噪比降低，但行为无明显损害。这些变化反映了精神分裂症患者所见的部分但不是全部神经生理学缺陷，表明其他神经元群体以及可能的大脑区域也参与其中。