The Salk Institute, Laboratory of Genetics, La Jolla, CA 92037, USA; University of California San Diego, Department of Neurosciences, La Jolla, CA 92093, USA.
The Salk Institute, Laboratory of Genetics, La Jolla, CA 92037, USA.
Stem Cell Reports. 2019 Sep 10;13(3):474-484. doi: 10.1016/j.stemcr.2019.08.001. Epub 2019 Aug 29.
Neuronal activity can be modeled as a nonlinear dynamical system to yield measures of neuronal state and dysfunction. The electrical recordings of stem cell-derived neurons from individuals with autism spectrum disorder (ASD) and controls were analyzed using minimum embedding dimension (MED) analysis to characterize their dynamical complexity. MED analysis revealed a significant reduction in dynamical complexity in ASD neurons during differentiation, which was correlated to bursting and spike interval measures. MED was associated with clinical endpoints, such as nonverbal intelligence, and was correlated with 53 differentially expressed genes, which were overrepresented with ASD risk genes related to neurodevelopment, cell morphology, and cell migration. Spatiotemporal analysis also showed a prenatal temporal enrichment in cortical and deep brain structures. Together, we present dynamical analysis as a paradigm that can be used to distinguish disease-associated cellular electrophysiological and transcriptional signatures, while taking into account patient variability in neuropsychiatric disorders.
神经元活动可以被建模为一个非线性动力系统，以产生神经元状态和功能障碍的度量。使用最小嵌入维数 (MED) 分析分析了来自自闭症谱系障碍 (ASD) 和对照组个体的干细胞衍生神经元的电记录，以表征它们的动力复杂性。MED 分析显示，在分化过程中，ASD 神经元的动力复杂性显著降低，这与爆发和尖峰间隔测量有关。MED 与非语言智力等临床终点相关，与 53 个差异表达基因相关，这些基因与与神经发育、细胞形态和细胞迁移相关的 ASD 风险基因呈过度表达。时空分析还显示皮质和深部脑结构在产前时间上存在富集。总之，我们提出动力分析作为一种范例，可以用于区分与疾病相关的细胞电生理和转录特征，同时考虑到神经精神疾病中患者的变异性。
