Assaying Spontaneous Network Activity and Cellular Viability Using Multi-well Microelectrode Arrays

  • Jasmine P. Brown
  • Brittany S. Lynch
  • Itaevia M. Curry-Chisolm
  • Timothy J. ShaferEmail author
  • Jenna D. Strickland
Part of the Methods in Molecular Biology book series (MIMB, volume 1601)


Microelectrode array (MEA) technology is a neurophysiological method that allows for the spontaneous measure of activity in neural cultures and determination of drug and chemical effects thereon. Recent introduction of multi-well MEA (mwMEA) formats have dramatically increased the throughput of this technology, allowing more efficient compound screening. Rapid characterization of compounds for neuroactivity or neurotoxicity hazard evaluation following acute, chronic, or developmental exposures ideally would also consider compound effects on cell health, and to do so in the same well requires a multiplexed approach. Procedures describing the multiplexed method to acute and developmental screening are described in this chapter.

Key words

Microelectrode array (MEA) Neurophysiological method mwMEA Developmental screening 



Preparation of this document has been funded by the U.S. Environmental Protection Agency. This document has been subjected to review by the National Health and Environmental Effects Research Laboratory and approved for publication. Approval does not signify that the contents reflect the views of the Agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use.

Jasmine P Brown is supported by Student Services Contracts EP-14-D-000101. Brittany S Lynch is an Oak Ridge Institute for Science and Education Fellow.


  1. 1.
    Valdivia P, Martin MT, Houck K, Lefew WR, Ross J, Shafer TJ (2014) Multi-well microelectrode array recordings detect neuroactivity of ToxCast compounds. Neurotoxicology 44:204–217CrossRefPubMedGoogle Scholar
  2. 2.
    Nicolas J, Hendriksen PJM, van Kleef RGDM, de Groot A, Bovee TFH, Rietjens IMCM, Westerink RHS (2014) Detection of marine neurotoxins in food safety testing using a multielectrode array. Mol Nutr Food Res 58:2369–2378CrossRefPubMedGoogle Scholar
  3. 3.
    Hogberg HT, Sobanski T, Novellino A, Whelan M, Weiss DG, Bal-Price AK (2011) Application of micro-electrode arrays (MEAs) as an emerging technology for developmental neurotoxicity: evaluation of domoic acid-induced effects in primary cultures of rat cortical neurons. Neurotoxicology 32:158–168CrossRefPubMedGoogle Scholar
  4. 4.
    Robinette BL, Harrill JA, Mundy WR, Shafer TJ (2011) In vitro assessment of developmental neurotoxicity: use of microelectrode arrays to measure functional changes in neuronal network ontogeny. Front Neuroeng 4:1CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Cotterill E, Hall D, Wallace K, Mundy WR, Eglen SJ, Shafer TJ (2016) Characterization of early cortical neural network development in multiwell microelectrode array plates. J Biomol Screen 21(5):510–519CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Johnstone AF, Gross GW, Weiss DG, Schroeder OH, Gramowski A, Shafer TJ (2010) Microelectrode arrays: a physiologically based neurotoxicity testing platform for the 21st century. Neurotoxicology 31:331–350CrossRefPubMedGoogle Scholar
  7. 7.
    Wallace K, Strickland JD, Valdivia P, Mundy WR, Shafer TJ (2015) A multiplexed assay for determination of neurotoxicant effects on spontaneous network activity and viability from microelectrode arrays. Neurotoxicology 49:79–85CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  • Jasmine P. Brown
    • 1
  • Brittany S. Lynch
    • 1
  • Itaevia M. Curry-Chisolm
    • 1
  • Timothy J. Shafer
    • 1
    Email author
  • Jenna D. Strickland
    • 2
    • 3
  1. 1.Integrated Systems Toxicology DivisionNHEERL, US EPA, MD105-05Research Triangle ParkUSA
  2. 2.Axion BiosystemsAtlantaUSA
  3. 3.Department of Pharmacology and ToxicologyMichigan State UniversityE. LansingUSA

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