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Novel approaches using the microelectrode array to measure network function in larval zebrafish (INA 2022)
Citation:
Martin, M., S. Padilla, K. Paul-Friedman, D. Herr, Steve Simmons, J. Hedge, AND T. Shafer. Novel approaches using the microelectrode array to measure network function in larval zebrafish (INA 2022). International Neurotoxicology Association (INA) Meeting 2022, Durham, North Carolina, May 16 - 22, 2022. https://doi.org/10.23645/epacomptox.20135990
Impact/Purpose:
Presentation to the International Neurotoxicology Association (INA) meeting which will be held in Durham, NC from May 16th - 22nd, 20222. Assessment of Developmental Neurotoxicity (DNT) using animal-based Guideline studies is expensive, time consuming, and does not always yield actionable data. Further, DNT assessment is not required under TSCA and the Guideline DNT study is a triggered study under FIFRA. Consequently, few of the tens of thousands of chemicals to which humans may be exposed have been evaluated for DNT hazard. To address this issue, New Approach Methodologies (NAMs) are being developed that can help provide data for risk decisions under FIFRA and TSCA. As these methods become more widely utilized, they can also provide information for other types of environmental decision-making as well.
Description:
Formation of neural networks is a fundamental neurodevelopmental process important for sensory, motor, and cognitive function. The microelectrode array (MEA) network formation assay is a tool being used as a developmental neurotoxicity (DNT) new approach methodology (NAM) that measures local field potentials and can evaluate changes in network formation due to developmental chemical exposure. Previously, we have used dissociated cortical cells from postnatal day 0 rat pups. Here we hope to expand upon this MEA network formation assay using multiple approaches. First, we plan to combine MEA technology with another DNT-related NAM, the zebrafish larval photomotor response assay. We plan to record brain activity from intact larval zebrafish at baseline and also during a dark to light transition period. This will allow us to connect neurophysiological responses to neurobehavioural responses. Second, we are currently utilizing human induced pluripotent stem cells (hIPSCs) and optogenetic tools in the MEAs. This will allow us to selectively activate excitatory or inhibitory neurons and then record the subsequent electrical activity from these stimulated cells, which could provide additional mechanistic data regarding chemical effects on developing networks. Together, these MEA-based approaches will hopefully help further develop the in vitro DNT NAM testing battery and allow us to better predict chemical effects on human health. The views expressed are those of the authors and do not necessarily reflect the views or policies of the US EPA.
URLs/Downloads:
DOI: Novel approaches using the microelectrode array to measure network function in larval zebrafish (INA 2022)
MMARTIN_INA_DNT_NAMS_WEBINAR_FINAL_STICS.PDF (PDF, NA pp, 2507.73 KB, about PDF)