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Analysis and Model of Cortical Slow Waves Acquired with Optical Techniques

机译:用光学技术获得皮质慢波的分析与模型

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摘要

Slow waves (SWs) are spatio-temporal patterns of cortical activity that occur both during natural sleep and anesthesia and are preserved across species. Even though electrophysiological recordings have been largely used to characterize brain states, they are limited in the spatial resolution and cannot target specific neuronal population. Recently, large-scale optical imaging techniques coupled with functional indicators overcame these restrictions, and new pipelines of analysis and novel approaches of SWs modelling are needed to extract relevant features of the spatio-temporal dynamics of SWs from these highly spatially resolved data-sets. Here we combined wide-field fluorescence microscopy and a transgenic mouse model expressing a calcium indicator (GCaMP6f) in excitatory neurons to study SW propagation over the meso-scale under ketamine anesthesia. We developed a versatile analysis pipeline to identify and quantify the spatio-temporal propagation of the SWs. Moreover, we designed a computational simulator based on a simple theoretical model, which takes into account the statistics of neuronal activity, the response of fluorescence proteins and the slow waves dynamics. The simulator was capable of synthesizing artificial signals that could reliably reproduce several features of the SWs observed in vivo, thus enabling a calibration tool for the analysis pipeline. Comparison of experimental and simulated data shows the robustness of the analysis tools and its potential to uncover mechanistic insights of the Slow Wave Activity (SWA).
机译:慢波(SWS)是在天然睡眠和麻醉期间发生的皮质活动的时空模式,并且在物种中被保存。尽管电生理记录主要用于表征脑状态,但它们的空间分辨率受到限制,不能靶向特定的神经元群。最近,与功能指示器耦合的大型光学成像技术克服了这些限制,并且需要新的SWS建模方法和新颖的SWS建模方法来提取来自这些高度空间解析的数据集的SWS的时空动态的相关特征。在这里,我们组合了广场荧光显微镜和在兴奋性神经元中表达钙指示剂(GCAMP6F)的转基因小鼠模型,以研究氯胺酮麻醉下的中间规模的SW繁殖。我们开发了一个多功能分析管道,以识别和量化SWS的时空传播。此外,我们设计了一种基于简单理论模型的计算模拟器,其考虑了神经元活动的统计,荧光蛋白的响应和慢波动力学。模拟器能够合成可以可靠地再现在体内观察到的SWS的若干特征的人工信号,从而使分析管道能够校准工具。实验和模拟数据的比较显示了分析工具的稳健性及其揭示慢波活动的机制洞察力(SWA)的潜力。

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