Herr David W
Neurological and Endocrine Toxicology Branch, Public Health and Integrated Toxicology Division, CPHEA/ORD, U.S. Environmental Protection Agency, Washington, NC, United States.
Front Toxicol. 2021 Dec 14;3(729788):1. doi: 10.3389/ftox.2021.729788.
Neuroelectrophysiology is an old science, dating to the 18th century when electrical activity in nerves was discovered. Such discoveries have led to a variety of neurophysiological techniques, ranging from basic neuroscience to clinical applications. These clinical applications allow assessment of complex neurological functions such as (but not limited to) sensory perception (vision, hearing, somatosensory function), and muscle function. The ability to use similar techniques in both humans and animal models increases the ability to perform mechanistic research to investigate neurological problems. Good animal to human homology of many neurophysiological systems facilitates interpretation of data to provide cause-effect linkages to epidemiological findings. Mechanistic cellular research to screen for toxicity often includes gaps between cellular and whole animal/person neurophysiological changes, preventing understanding of the complete function of the nervous system. Building Adverse Outcome Pathways (AOPs) will allow us to begin to identify brain regions, timelines, neurotransmitters, etc. that may be Key Events (KE) in the Adverse Outcomes (AO). This requires an integrated strategy, from to (and hypothesis generation, testing, revision). Scientists need to determine intermediate levels of nervous system organization that are related to an AO and work both upstream and downstream using mechanistic approaches. Possibly more than any other organ, the brain will require networks of pathways/AOPs to allow sufficient predictive accuracy. Advancements in neurobiological techniques should be incorporated into these AOP-base neurotoxicological assessments, including interactions between many regions of the brain simultaneously. Coupled with advancements in optogenetic manipulation, complex functions of the nervous system (such as acquisition, attention, sensory perception, etc.) can be examined in real time. The integration of neurophysiological changes with changes in gene/protein expression can begin to provide the mechanistic underpinnings for biological changes. Establishment of linkages between changes in cellular physiology and those at the level of the AO will allow construction of biological pathways (AOPs) and allow development of higher throughput assays to test for changes to critical physiological circuits. To allow mechanistic/predictive toxicology of the nervous system to be protective of human populations, neuroelectrophysiology has a critical role in our future.
神经电生理学是一门古老的科学，可追溯到18世纪神经电活动被发现之时。此类发现催生了各种各样的神经生理学技术，涵盖从基础神经科学到临床应用的诸多领域。这些临床应用能够评估复杂的神经功能，比如（但不限于）感觉知觉（视觉、听觉、躯体感觉功能）以及肌肉功能。在人类和动物模型中运用相似技术的能力增强了开展机制性研究以探究神经问题的能力。许多神经生理系统在动物与人类之间具有良好的同源性，这便于对数据进行解读，从而为流行病学研究结果提供因果联系。用于筛选毒性的机制性细胞研究常常存在细胞层面与整个动物/人体神经生理变化之间的脱节，阻碍了对神经系统完整功能的理解。构建不良结局路径（AOP）将使我们能够开始识别可能是不良结局（AO）中的关键事件（KE）的脑区、时间线、神经递质等。这需要一种综合策略，从[此处原文缺失相关内容]到[此处原文缺失相关内容]（以及假设生成、测试、修订）。科学家需要确定与不良结局相关的神经系统组织的中间层次，并使用机制性方法在上下游展开研究。或许比任何其他器官都更甚的是，大脑将需要路径/不良结局路径网络，以实现足够的预测准确性。神经生物学技术的进步应被纳入这些基于不良结局路径的神经毒理学评估之中，包括同时考察大脑多个区域之间的相互作用。结合光遗传学操纵技术的进步，可以实时检测神经系统的复杂功能（如习得、注意力、感觉知觉等）。将神经生理变化与基因/蛋白质表达变化相结合，能够开始为生物学变化提供机制基础。建立细胞生理学变化与不良结局层面变化之间的联系，将有助于构建生物学路径（不良结局路径），并有助于开发更高通量的检测方法，以测试关键生理回路的变化。为使神经系统的机制性/预测性毒理学能够保护人类群体，神经电生理学在我们的未来将发挥关键作用。
