Tau is a predominantly neuronal protein that is normally bound to microtubules, where it acts to modulate neuronal and axonal stability. In humans, pathological forms of tau are implicated in a range of diseases that are collectively known as tauopathies. Kinases and phosphatases are responsible for maintaining the correct balance of tau phosphorylation to enable axons to be both stable and labile enough to function properly. In the early stages of tauopathies, this balance is interrupted leading to dissociation of tau from microtubules. This leaves microtubules prone to damage and phosphorylated tau prone to aggregation. Initially, phosphorylated tau forms oligomers, then fibrils, and ultimately neurofibrillary tangles (NFTs). It is widely accepted that the initial soluble oligomeric forms of tau are probably the most pathologically relevant species but there is relatively little quantitative information to explain exactly what their toxic effects are at the individual neuron level. Electrophysiology provides a valuable tool to help uncover the mechanisms of action of tau oligomers on synaptic transmission within single neurons. Understanding the concentration-, time-, and neuronal compartment-dependent actions of soluble tau oligomers on neuronal and synaptic properties are essential to understanding how best to counteract its effects and to develop effective treatment strategies. Here, we briefly discuss the standard approaches used to elucidate these actions, focusing on the advantages and shortcomings of the experimental procedures. Subsequently, we will describe a new approach that addresses specific challenges with the current methods, thus allowing real-time toxicity evaluation at the single-neuron level.

Tau是一种主要是神经元蛋白，通常与微管结合，在其中调节神经元和轴突的稳定性。在人类中，tau的病理形式与多种疾病有关，这些疾病统称为tauopathies。激酶和磷酸酶负责维持tau磷酸化的正确平衡，以使轴突既稳定又不稳定，足以正常运行。在tauopathies的早期阶段，这种平衡被中断，导致tau从微管解离。这使微管易于损坏，磷酸化的tau易于聚集。最初，磷酸化的tau形成低聚物，然后形成原纤维，最终形成神经原纤维缠结（NFT）。人们普遍认为，tau的最初可溶性低聚形式可能是与病理最相关的物种，但是相对缺乏定量信息来确切解释其在单个神经元水平上的毒性作用。电生理学提供了宝贵的工具，可帮助揭示tau低聚物对单个神经元内突触传递的作用机理。了解可溶性tau低聚物对神经元和突触特性的浓度，时间和神经元区室依赖性作用，对于了解如何最好地抵消其作用和制定有效的治疗策略至关重要。在这里，我们简要讨论用于阐明这些动作的标准方法，重点是实验程序的优缺点。后来，