Citation:

Shafer, Tim. Application of Microelectrode Array Approaches to Neurotoxicity Testing and Screening. Chapter 12, In vitro neuronal networksI. Springer, New York, NY, 22:275-297, (2019). https://doi.org/10.1007/978-3-030-11135-9_12

Impact/Purpose:

There is a need for rapid and economical approaches to testing and prioritizing large numbers of compounds for the potential to cause neurotoxicity and developmental neurotoxicity. One approach to accomplishing this is to grow neural cultures "in the dish" on top of arrays of microelectrodes that can measure the activity of the resulting neural networks. Chemicals can be added to the dish to determine how they alter the activity or the formation of these networks. This chapter provides an overview of the basic information needed to conduct these experiments in the laboratory

Description:

The nervous system, and especially the developing nervous system, is uniquely sensitive to perturbation by a wide variety of natural toxins, drugs, and a wide range of environmental chemicals (metals, pesticides, solvents, etc). The nervous system is unique from other organ systems (such as the liver, kidney and lungs) due to the nature of its function; it must receive input from the environment, rapidly transmit that information over long distances, integrate information from multiple sources, store it and generate appropriate responses. This is accomplished through the rapid transition of biochemical to electrical signals (and vice-versa) and through spatio-temporal patterns of electrical signals to encode and convey information within networks of interconnected neurons and to target tissues (e.g. smooth and skeletal muscle, endocrine glands). Small networks of interconnected neurons are critical to nervous system function. These networks often exhibit synchronous and oscillatory behavior, which when disrupted are associated with pathological disease, including schizophrenia, epilepsy, autism and neurodegenerative diseases. Because the field of microelectrode array recording evolved later than other electrophysiological approaches, much less is known about how neurotoxicants alter function at the level of neuronal networks. However, MEAs have a unique niche in the neurotoxicologist’s toolbox, as they alone facilitate the evaluation of how chemicals alter the function of small networks of interconnected neurons. One way that this approach is contributing to our knowledge is by providing additional mechanistic information on the actions of compounds on neural networks. A second, and perhaps more important way that MEA approches are impacting the field of neurotoxicity is in the screening of compounds for their potential to cause neurotoxicity or developmental neurotoxicity. The lack of information on these endpoints for thousands of chemicals has resulted in an urgent need for rapid and economical approaches to address this data gap, which can in part be filled by MEA approaches. As such, the role of MEAs in neurotoxicity screening has been an area of considerable growth in the last decade and will be further addressed below. In this chapter, I will present an overview of how neural networks cultured on MEAs have been used to address both mechanistic questions and screening approaches related to neurotoxicity testing. I will discuss some important methodological considerations of using MEAs for this purpose, as my experience has been that good methodology is critical too btaining usable screening data. Finally, I will also present some challenges for the future; better utilization of the rich information in MEA recordings and better incorporation of neural networks derived from humans into neurotoxicity studies with MEAs.

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