Alterations in Schizophrenia-Associated Genes Can Lead to Increased Power in Delta Oscillations
Alterations in Schizophrenia-Associated Genes Can Lead to Increased Power in Delta Oscillations
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DOI：
10.1093/cercor/bhy291
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发表时间：
2019-02-01
期刊：
影响因子：
3.7
通讯作者：
Einevoll, Gaute T.
中科院分区：
文献类型：
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作者：
Maki-Marttunen, Tuomo;Krull, Florian;Einevoll, Gaute T.
全基因组关联研究表明，许多离子通道与精神分裂症的病理生理学有关。虽然这些通道的功能在单细胞研究中表现得相对较好，但这些通道中的共同变异对精神分裂症的神经生理生物标记物和症状的贡献仍然难以捉摸。在这里，利用计算模型，我们表明精神分裂症的一个常见的生物标志物，即增量振荡功率的增加，可能是电压门控离子通道或钙转运体表达或动力学改变的直接结果。我们的V层锥体细胞电路模型突出了多种类型的精神分裂症相关变异，这些变异有助于改变增量频段的动力学。此外，我们的模型预测，增加V层锥体细胞网络增益和对增量频率振荡的反应的相同的膜机制也可能导致脉冲前抑制的单细胞相关性缺陷，脉冲前抑制是一种与精神分裂症高度相关的行为生物标志物。
Genome-wide association studies have implicated many ion channels in schizophrenia pathophysiology. Although the functions of these channels are relatively well characterized by single-cell studies, the contributions of common variation in these channels to neurophysiological biomarkers and symptoms of schizophrenia remain elusive. Here, using computational modeling, we show that a common biomarker of schizophrenia, namely, an increase in delta-oscillation power, may be a direct consequence of altered expression or kinetics of voltage-gated ion channels or calcium transporters. Our model of a circuit of layer V pyramidal cells highlights multiple types of schizophrenia-related variants that contribute to altered dynamics in the delta-frequency band. Moreover, our model predicts that the same membrane mechanisms that increase the layer V pyramidal cell network gain and response to delta-frequency oscillations may also cause a deficit in a single-cell correlate of the prepulse inhibition, which is a behavioral biomarker highly associated with schizophrenia.