Background Micro-Electrode Array (MEA) technology allows researchers to perform long-term non-invasive neuronal recordings in-vitro while actively interacting with the cultured neurons. Despite numerous studies carried out using MEAs, many functional, chemical and structural mechanisms of how dissociated cortical neurons develop and respond to external stimuli are not yet well understood because of the lack of quantitative studies that assess how their development can be affected by chronic external stimulation. Methods To investigate network changes, we analyzed a large MEA data set composed of neuron spikes recorded from cultures of dissociated rat cortical neurons plated on MEA dishes with 59 recording electrodes each. Neural network activity was recorded during the first five weeks of each culture’s in-vitro development. Stimulation sessions were delivered to each of the 59 electrodes. The False Discovery Rate technique was used to quantify the temporal evolution of dissociated cortical neurons. Our analysis focused on network responses that occurred within selected time window durations, namely 50 ms, 100 ms and 150 ms after stimulus onset. Results Our results show an evolution in dissociated cortical neuronal network activity over time, that reflects the network synaptic evolution. Furthermore, we tested the sensitivity of our technique to different observation time windows and found that varying the time windows, allows us to capture different dynamics of the observed responses. In addition, when selecting a 150 ms observation time window, our findings indicate that cultures dissociated from the same brain tissue display trends in their temporal evolution that are more similar than those obtained from different brains. Conclusion Our results emphasize that the FDR technique can be implemented without the need to make any particular assumptions about the data a priori. The proposed technique was able to capture the well-known dissociated cortical neuron networks’ temporal evolution, that has been previously observed in in-vivo and in intact brain tissue studies. Furthermore, our findings suggest that the time window that is used to capture the stimulus-evoked network responses is a critical parameter to analyze the electrical behavioral and temporal evolution of dissociated cortical neurons.
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机译：背景技术微电极阵列（MEA）技术允许研究人员在体外进行长期无侵入性神经元记录，同时主动与培养的神经元相互作用。尽管使用MEAS进行了许多研究，但由于缺乏评估其发育如何受慢性外部刺激的影响，因此尚未充分理解如何对外部刺激的多种功能，化学和结构机制进行多种研究，因此尚未充分理解。 。研究网络变化的方法，我们分析了由从在MEA盘上铺设在MEA盘上的解离大鼠皮质神经元的培养物中记录的神经元尖峰组成的大型MEA数据集。在每个文化在体外发育的前五个星期内记录神经网络活动。刺激会话被传送到59个电极中的每一个。假发现率技术用于量化解离皮质神经元的时间演变。我们的分析专注于在选定的时间窗口持续时间内发生的网络响应，即刺激发作后50 ms，100 ms和150毫秒。结果我们的结果表明，随着时间的推移，对解离皮质神经元网络活动的演变，这反映了网络突触演进。此外，我们测试了我们技术对不同观察时间窗口的敏感性，发现改变时间窗口，允许我们捕获观察到的响应的不同动态。 In addition, when selecting a 150 ms observation time window, our findings indicate that cultures dissociated from the same brain tissue display trends in their temporal evolution that are more similar than those obtained from different brains.结论我们的结果强调可以实施FDR技术，而无需对数据进行任何特定的假设。所提出的技术能够捕获众所周知的解离皮质神经元网络的颞型进化，其先前在体内和完整的脑组织研究中观察到。此外，我们的研究结果表明，用于捕获刺激的网络响应的时间窗口是分析解离皮质神经元的电学行为和时间演进的关键参数。
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