Data from: Recurrently connected and localized neuronal communities initiate coordinated spontaneous activity in neuronal networks

Developing neuronal systems intrinsically generate coordinated spontaneous activity that propagates by involving a large number of synchronously firing neurons. In vivo, waves of spikes transiently characterize the activity of developing brain circuits and are fundamental for activity-dependent circuit formation. In vitro, coordinated spontaneous spiking activity, or network bursts (NBs), interleaved within periods of asynchronous spikes emerge during the development of 2D and 3D neuronal cultures. Several studies have investigated this type of activity and its dynamics, but how a neuronal system generates these coordinated events remains unclear. Here, we investigate at a cellular level the generation of network bursts in spontaneously active neuronal cultures by exploiting high-resolution multielectrode array recordings and computational network modelling. Our analysis reveals that NBs are generated in specialized regions of the network (functional neuronal communities) that feature neuronal links with high cross-correlation peak values, sub-millisecond lags and that share very similar structural connectivity motifs providing recurrent interactions. We show that the particular properties of these local structures enable locally amplifying spontaneous asynchronous spikes and that this mechanism can lead to the initiation of NBs. Through the analysis of simulated and experimental data, we also show that AMPA currents drive the coordinated activity, while NMDA and GABA currents are only involved in shaping the dynamics of NBs. Overall, our results suggest that the presence of functional neuronal communities with recurrent local connections allows a neuronal system to generate spontaneous coordinated spiking activity events. As suggested by the rules used for implementing our computational model, such functional communities might naturally emerge during network development by following simple constraints on distance-based connectivity.

发育中的神经元系统可自发产生协同性自发放电活动，该活动通过大量同步放电的神经元参与实现传播。在体（in vivo）条件下，锋电位（spike）波会短暂作为发育中脑环路活动的标志性特征，且对依赖活动的环路构建过程具有关键作用。离体（in vitro）环境中，协同性自发放电活动（或称网络锋电位爆发（network bursts, NBs））会穿插于异步锋电位发放时段之间，并在二维与三维神经元培养体系的发育过程中出现。已有多项研究对这类活动及其动力学特性展开了探索，但神经元系统如何产生这类协同性放电事件的机制仍不明确。本研究依托高分辨率多电极阵列（multielectrode array, MEA）记录与计算网络建模技术，从细胞层面解析了自发放电神经元培养体系中网络锋电位爆发的产生机制。分析结果表明，网络锋电位爆发产生于神经网络中的特化区域——功能神经元集群（functional neuronal communities），这类区域具备神经元连接具有高互相关峰值、亚毫秒级时间延迟，且共享高度相似的提供循环交互作用的结构连接基序。本研究证实，这类局部结构的独特特性可实现对局部自发性异步锋电位的放大，且该机制能够触发网络锋电位爆发的启动。通过对模拟数据与实验数据的分析，本研究还发现，AMPA电流可驱动协同性活动，而NMDA与GABA电流仅参与调控网络锋电位爆发的动力学特性。综上，本研究结果表明，具备局部循环连接的功能神经元集群的存在，使得神经元系统能够产生自发性协同锋电位放电活动事件。正如本研究计算模型的构建规则所揭示的，这类功能神经元集群或许可在网络发育过程中，通过遵循基于距离的连接的简单约束条件自然形成。