星形胶质细胞调控的可塑性神经元网络的癫痫样同步及其转迁机制研究

Recently, astrocytes have been of great interest in the study of synaptic plasticity, neural network regulation and neurological disorders such as epilepsy. By using synchronization and bifurcation theory of nonlinear dynamical systems and complex network, together with numerical simulation, this research will investigate the epileptic dynamics modeling analysis for plastic neuronal network with astrocytic regulation. And the generation, propagation and termination and their transition dynamics of epileptiform synchronization of the proposed model will be explored to uncover the internal relationship between the bifurcation dynamics of the coupled systems and the transition dynamics which is of the regular discharges and synchronous epileptiform discharges. Moreover, under the electric effect and astrocytic regulation the dynamical control strategies of epileptiform synchronization modes in the plastic neuronal network models will be analyzed to further obtain the best stimulation paradigm to control epileptiform rhythms. Through the analysis and prediction of the above issues, our results are expected to offer us a profound understanding of more novel regulatory mechanisms of astrocytic involvement in epileptic seizures, provide scientific and reliable theoretical guidance for the diagnosis and treatment of epilepsy, and promote the development of nonlinear dynamics and network science.

近年来，星形胶质细胞在突触可塑性、神经网络调控和诸如癫痫等神经系统疾病等研究中备受关注。本项目利用非线性动力系统的同步和分岔理论以及复杂网络理论，结合数值仿真，开展星形胶质细胞调控的可塑性神经元网络癫痫动力学建模分析，研究模型的癫痫样同步形成、传播和消失及其转迁动力学行为，揭示正常放电与同步癫痫样放电模式之间转迁动力学与耦合系统分岔动力学的内在联系；分析电效应和星形胶质细胞调控下可塑性神经元网络模型呈现的癫痫样同步模式的动力学控制策略，得到控制癫痫样节律的最优刺激范式。通过上述问题的分析和预测结果，可深入理解星形胶质细胞在癫痫发作中更多新的调控机制，为癫痫的临床诊断和治疗提供理论指导，并推动非线性动力学和网络科学的发展。

本项目构建了若干星形胶质细胞网络和神经元-星形胶质细胞网络等动力学模型作为研究对象，利用非线性系统的分岔控制和复杂网络理论，得到星形胶质细胞和神经元动力学行为的若干调控机理，以及电刺激下癫痫神经网络的最优控制机制。具体来说，研究成果包括：（1）得到星形胶质细胞在信息交互过程中形成的包含自发性和诱导性钙振荡机理，确定了耦合神经元系统的稳态同步激发模式与非对称激励之间的关系，且所得建模方法应用于复杂网络的一致性和随机游走研究之中。（2）确定了癫痫神经网络下星形胶质细胞动力学调控的潜在靶点，且分析手段应用于急性髓性白血病动力学模型和基因调控模型中得到了丰富的分岔动力学。（3）分析了星形胶质细胞调控下网络同步癫痫样活动产生、传播和消失的电刺激调控机制，确定了最优刺激范式下的星形胶质细胞的动力学潜在控制靶点。这些研究结果加深了对星形胶质细胞在癫痫发作中潜在调控靶点的认识。项目执行期间，共发表科技论文4篇，其中SCI论文3篇，联合培养1名硕士研究生毕业。