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DOI10.1016/j.taap.2018.01.017
Defining toxicological tipping points in neuronal network development
Frank, Christopher L.1; Brown, Jasmine P.1; Wallace, Kathleen1; Wambaugh, John F.2; Shah, Imran2; Shafer, Timothy J.1
发表日期2018-09-01
ISSN0041-008X
卷号354页码:81-93
英文摘要

Measuring electrical activity of neural networks by microelectrode array (MEA) has recently shown promise for screening level assessments of chemical toxicity on network development and function. Important aspects of interneuronal communication can be quantified from a single MEA recording, including individual firing rates, coordinated bursting, and measures of network synchrony, providing rich datasets to evaluate chemical effects. Further, multiple recordings can be made from the same network, including during the formation of these networks in vitro. The ability to perform multiple recording sessions over the in vitro development of network activity may provide further insight into developmental effects of neurotoxicants. In the current study, a recently described MEA-based screen of 86 compounds in primary rat cortical cultures over 12 days in vitro was revisited to establish a framework that integrates all available primary measures of electrical activity from MEA recordings into a composite metric for deviation from normal activity (total scalar perturbation). Examining scalar perturbations over time and increasing concentration of compound allowed for definition of critical concentrations or "tipping points" at which the neural networks switched from recovery to non-recovery trajectories for 42 compounds. These tipping point concentrations occurred at predominantly lower concentrations than those causing overt cell viability loss or disrupting individual network parameters, suggesting tipping points may be a more sensitive measure of network functional loss. Comparing tipping points for six compounds with plasma concentrations known to cause developmental neurotoxicity in vivo demonstrated strong concordance and suggests there is potential for using tipping points for chemical prioritization.


英文关键词Network development;In vitro;Tipping point;Screening
语种英语
WOS记录号WOS:000442335500009
来源期刊TOXICOLOGY AND APPLIED PHARMACOLOGY
来源机构美国环保署
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/56430
作者单位1.US EPA, Integrated Syst Toxicol Div, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA;
2.US EPA, Natl Ctr Computat Toxicol, Res Triangle Pk, NC 27711 USA
推荐引用方式
GB/T 7714
Frank, Christopher L.,Brown, Jasmine P.,Wallace, Kathleen,et al. Defining toxicological tipping points in neuronal network development[J]. 美国环保署,2018,354:81-93.
APA Frank, Christopher L.,Brown, Jasmine P.,Wallace, Kathleen,Wambaugh, John F.,Shah, Imran,&Shafer, Timothy J..(2018).Defining toxicological tipping points in neuronal network development.TOXICOLOGY AND APPLIED PHARMACOLOGY,354,81-93.
MLA Frank, Christopher L.,et al."Defining toxicological tipping points in neuronal network development".TOXICOLOGY AND APPLIED PHARMACOLOGY 354(2018):81-93.
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