Department of Physiology, University of Auckland, Auckland, New Zealand.
Centre for Brain Research, University of Auckland, New Zealand.
J Neurophysiol. 2020 Mar 1;123(3):945-965. doi: 10.1152/jn.00411.2019. Epub 2020 Jan 29.
The human brain shows remarkable complexity in its cellular makeup and function, which are distinct from nonhuman species, signifying the need for human-based research platforms for the study of human cellular neurophysiology and neuropathology. However, the use of adult human brain tissue for research purposes is hampered by technical, methodological, and accessibility challenges. One of the major problems is the limited number of in vitro systems that, in contrast, are readily available from rodent brain tissue. With recent advances in the optimization of protocols for adult human brain preparations, there is a significant opportunity for neuroscientists to validate their findings in human-based systems. This review addresses the methodological aspects, advantages, and disadvantages of human neuron in vitro systems, focusing on the unique properties of human neurons and synapses in neocortical microcircuits. These in vitro models provide the incomparable advantage of being a direct representation of the neurons that have formed part of the human brain until the point of recording, which cannot be replicated by animal models nor human stem-cell systems. Important distinct cellular mechanisms are observed in human neurons that may underlie the higher order cognitive abilities of the human brain. The use of human brain tissue in neuroscience research also raises important ethical, diversity, and control tissue limitations that need to be considered. Undoubtedly however, these human neuron systems provide critical information to increase the potential of translation of treatments from the laboratory to the clinic in a way animal models are failing to provide.
人类大脑在细胞组成和功能上表现出显著的复杂性，与非人类物种不同，这表明需要基于人类的研究平台来研究人类细胞神经生理学和神经病理学。然而，由于技术、方法和可及性方面的挑战，使用成人脑组织进行研究受到了阻碍。其中一个主要问题是，与啮齿动物脑组织相比，可用于研究的体外系统数量有限。随着优化成人脑组织制备协议的最新进展，神经科学家有机会在基于人类的系统中验证他们的发现。本综述讨论了人类神经元体外系统的方法学方面、优点和缺点，重点介绍了新皮层微电路中人类神经元和突触的独特特性。这些体外模型提供了无与伦比的优势，即直接代表了在记录点之前已构成人脑一部分的神经元，这是动物模型或人类干细胞系统无法复制的。在人类神经元中观察到重要的独特细胞机制，这些机制可能是人类大脑更高阶认知能力的基础。在神经科学研究中使用人类脑组织也引发了重要的伦理、多样性和对照组织限制问题，需要加以考虑。然而，这些人类神经元系统提供了关键信息，增加了将治疗方法从实验室转化为临床的潜力，而这是动物模型无法提供的。
