Homeostatic regulation of neuronal activity is essential for robust computation; set-points, such as firing rate, are actively stabilized to compensate for perturbations. The disruption of brain function central to neurodegenerative disease likely arises from impairments of computationally essential set-points. Here, we systematically investigated the effects of tau-mediated neurodegeneration on all known set-points in neuronal activity. We continuously tracked hippocampal neuronal activity across the lifetime of a mouse model of tauopathy. We were unable to detect effects of disease in measures of single-neuron firing activity. By contrast, as tauopathy progressed, there was disruption of network-level neuronal activity, quantified by measuring neuronal pairwise interactions and criticality, a homeostatically controlled, ideal computational regime. Deviations in criticality correlated with symptoms, predicted underlying anatomical pathology, occurred in a sleep-wake-dependent manner, and could be used to reliably classify an animal’s genotype. This work illustrates how neurodegeneration may disrupt the computational capacity of neurobiological systems.

中文翻译：

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群体失败：尽管组成神经元保持稳定，但 tau 蛋白病会破坏紧急动力学中的稳态设定点


神经元活动的稳态调节对于稳健计算至关重要;设定点 （例如发射速率） 会主动稳定以补偿扰动。神经退行性疾病的核心大脑功能的破坏可能是由于计算基本设定点的损害引起的。在这里，我们系统地研究了 tau 介导的神经变性对神经元活动中所有已知设定点的影响。我们在 tau 蛋白病小鼠模型的生命周期中持续跟踪海马神经元活动。我们无法检测疾病对单神经元放电活动测量的影响。相比之下，随着 tau 蛋白病的进展，网络水平神经元活动受到破坏，通过测量神经元成对相互作用和临界性（一种稳态控制的理想计算机制）来量化。临界度的偏差与症状相关，预测潜在的解剖病理，以睡眠-觉醒依赖性方式发生，可用于可靠地对动物的基因型进行分类。这项工作说明了神经退行性变如何破坏神经生物学系统的计算能力。