Inhibition of 14-3-3 Proteins Alters Neural Oscillations in Mice.

Inhibition of 14-3-3 Proteins Alters Neural Oscillations in Mice.
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DOI:
10.3389/fncir.2021.647856
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发表时间:
2021
影响因子:
3.5
通讯作者:
Zhou Y
Zhou Y
中科院分区:
医学3区
文献类型:
--
作者:
Jones ZB;Zhang J;Wu Y;Zhou Y

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越来越多的证据表明,精神分裂症是一种大脑沟通障碍,是功能和结构失调的结果。精神分裂症患者表现出不规则的神经元回路和网络活动,但这种活动的原因和后果仍然很大程度上未知。抑制小鼠大脑中的 14-3-3 蛋白会导致多种精神分裂症内表型的表达。在这里,我们研究了 14-3-3 抑制如何改变小鼠海马体 (HPC) 和前额皮质 (PFC) 中的神经元网络活动,这两个区域是与精神分裂症病理生理学有关的关键大脑区域。我们在这两个区域植入单极记录电极,以记录休息时和认知任务期间的局部场电位。通过对频带功率、相干性和相位幅度耦合的评估,我们发现 θ 和伽马频率范围内的神经振荡因 14-3-3 功能障碍而改变。利用转基因和病毒小鼠模型分别评估慢性和急性 14-3-3 抑制对振荡活动的影响,我们观察到两个模型之间的一些基本相似点和差异。我们将病毒介导的 14-3-3 蛋白抑制定位于 HPC 或 PFC,从而使我们能够评估每个区域对观察到的神经振荡变化的个体贡献。这些发现确定了 14-3-3 蛋白在神经振荡中的新作​​用,这可能对我们理解精神分裂症神经生物学有影响。
Accumulating evidence suggests that schizophrenia is a disorder of the brain’s communication, a result of functional and structural dysconnectivities. Patients with schizophrenia exhibit irregular neuronal circuit and network activity, but the causes and consequences of such activity remain largely unknown. Inhibition of 14-3-3 proteins in the mouse brain leads to the expression of multiple schizophrenia endophenotypes. Here we investigated how 14-3-3 inhibition alters neuronal network activity in the mouse hippocampus (HPC) and prefrontal cortex (PFC), key brain regions implicated in schizophrenia pathophysiology. We implanted monopolar recording electrodes in these two regions to record local field potentials both at rest and during a cognitive task. Through our assessment of band power, coherence, and phase-amplitude coupling, we found that neural oscillations in the theta and gamma frequency ranges were altered as a result of 14-3-3 dysfunction. Utilizing transgenic and viral mouse models to assess the effects of chronic and acute 14-3-3 inhibition on oscillatory activities, respectively, we observed several fundamental similarities and differences between the two models. We localized viral mediated 14-3-3 protein inhibition to either the HPC or PFC, allowing us to assess the individual contributions of each region to the observed changes in neural oscillations. These findings identify a novel role of 14-3-3 proteins in neural oscillations that may have implications for our understanding of schizophrenia neurobiology.
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