Inhibitory interneurons regulate the oscillatory rhythms and network synchrony that are required for cognitive functions and disrupted in Alzheimer's disease (AD). Network dysrhythmias in AD and multiple neuropsychiatric disorders are associated with hypofunction of Nav1.1, a voltage-gated sodium channel subunit predominantly expressed in interneurons. We show that Nav1.1-overexpressing, but not wild-type, interneuron transplants derived from the embryonic medial ganglionic eminence (MGE) enhance behavior-dependent gamma oscillatory activity, reduce network hypersynchrony, and improve cognitive functions in human amyloid precursor protein (hAPP)-transgenic mice, which simulate key aspects of AD. Increased Nav1.1 levels accelerated action potential kinetics of transplanted fast-spiking and non-fast-spiking interneurons. Nav1.1-deficient interneuron transplants were sufficient to cause behavioral abnormalities in wild-type mice. We conclude that the efficacy of interneuron transplantation and the function of transplanted cells in an AD-relevant context depend on their Nav1.1 levels. Disease-specific molecular optimization of cell transplants may be required to ensure therapeutic benefits in different conditions.

中文翻译：

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Nav1.1过表达的Interneuron移植可恢复阿尔茨海默氏病小鼠模型的脑节律和认知能力。

抑制性中间神经元调节认知功能所需并在阿尔茨海默氏病（AD）中中断的振荡节律和网络同步性。AD的网络节律不齐和多种神经精神疾病与Nav1.1的功能低下有关，Nav1.1是电压门控的钠通道亚单位，主要在中间神经元中表达。我们表明，从胚胎内侧神经节突起（MGE）衍生的Nav1.1过表达，但不是野生型的interneuron移植增强行为依赖的伽马振荡活性，减少网络超合，并改善人类淀粉样蛋白前体蛋白（hAPP）的认知功能）-转基因小鼠，可模拟AD的关键方面。Nav1.1水平的提高加速了快速加标和非快速加标的中间神经元的动作电位动力学。导航1。1缺陷的神经元间移植足以引起野生型小鼠的行为异常。我们得出结论，在与AD相关的情况下，中间神经元移植的功效和移植细胞的功能取决于其Nav1.1水平。细胞移植的疾病特异性分子优化可能需要确保在不同条件下的治疗益处。