Department of Electronics, Graduate School of Engineering, Tohoku Institute of Technology, 35-1 Yagiyama Kasumicho, Taihaku-ku, Sendai, Miyagi, 982-8577, Japan.
Department of Electronics, Graduate School of Engineering, Tohoku Institute of Technology, 35-1 Yagiyama Kasumicho, Taihaku-ku, Sendai, Miyagi, 982-8577, Japan; Advanced Institute for Materials Research, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, Miyagi, 982-8577, Japan; Japan Society for the Promotion of Science, Japan.
Biochem Biophys Res Commun. 2018 Mar 4;497(2):612-618. doi: 10.1016/j.bbrc.2018.02.117. Epub 2018 Feb 16.
Human induced pluripotent stem cell-derived neurons are promising for use in toxicity evaluations in nonclinical studies. The multi-electrode array (MEA) assay is used in such evaluation systems because it can measure the electrophysiological function of a neural network noninvasively and with high throughput. Synchronized burst firing (SBF) is the main analytic parameter of pharmacological effects in MEA data, but an accurate method for detecting SBFs has not been established. In this study, we present a 4-step method that accurately detects a target SBF confirmed by the researcher's interpretation of a raster plot. This method calculates one set parameter per step, in the following order: the inter-spike interval (ISI), the number of spikes in an SBF, the inter-SBF interval, and the number of spikes in an SBF again. We found that the 4-step method is advantageous over the conventional method because it determines the preferable duration of an SBF, accurately distinguishes continuous SBFs, detects weak SBFs, and avoids false detection of SBFs. We found also that pharmacological evaluations involving SBF analysis may differ depending on whether the 4-step or conventional threshold method is used. This 4-step method may contribute to improving the accuracy of drug toxicity and efficacy evaluations using human induced pluripotent stem cell-derived neurons.
人诱导多能干细胞衍生神经元有望用于非临床研究中的毒性评估。多电极阵列 (MEA) 测定法用于此类评估系统，因为它可以非侵入性且高通量地测量神经网络的电生理功能。同步爆发放电 (SBF) 是 MEA 数据中药物作用的主要分析参数，但尚未建立准确检测 SBF 的方法。在这项研究中，我们提出了一种 4 步方法，该方法可以准确检测到研究人员通过光栅图解释确认的目标 SBF。该方法按以下顺序为每个步骤计算一组参数： 脉冲间隔 (ISI)、SBF 中的脉冲数、SBF 之间的间隔以及 SBF 中的脉冲数。我们发现，4 步方法优于传统方法，因为它确定了 SBF 的优选持续时间，准确地区分了连续的 SBF，检测了较弱的 SBF，并避免了 SBF 的误检。我们还发现，涉及 SBF 分析的药理学评估可能因使用 4 步或传统阈值方法而有所不同。这种 4 步方法可能有助于提高使用人诱导多能干细胞衍生神经元进行药物毒性和疗效评估的准确性。
