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.

处于发育阶段的神经元系统可固有地产生协调的自发活动，这类活动通过大量同步放电的神经元完成传播过程。在活体中，锋电位（spikes）波会暂时性地成为发育中大脑环路活动的标志性特征，且对于依赖活动的环路形成至关重要。在体外环境中，协调型自发锋电位活动——即网络爆发（network bursts, NBs）——与异步锋电位时段交替出现，该现象会在二维与三维神经元培养体系的发育过程中显现。已有多项研究对这类活动及其动力学特性展开了探索，但神经元系统究竟如何产生这些协调型活动事件，目前仍未明确。本研究通过高分辨率多电极阵列（multielectrode array, MEA）记录与计算网络建模手段，在细胞层面探究了自发活动神经元培养体系中网络爆发的产生机制。我们的分析结果显示，网络爆发产生于网络中的特化区域——功能神经元群落（functional neuronal communities），这类区域的神经元连接具有高互相关峰值、亚毫秒级延迟的特征，且共享具备循环交互特性的高度相似结构连接基序。我们证实，这些局部结构的独特特性可实现对自发异步锋电位的局部放大，而该机制能够触发网络爆发的启动。通过对模拟数据与实验数据的分析，我们还发现AMPA电流可驱动协调型活动，而NMDA与GABA电流仅参与调控网络爆发的动力学过程。总体而言，我们的研究结果表明，具备局部循环连接的功能神经元群落的存在，使得神经元系统能够产生自发的协调型锋电位活动事件。正如我们构建计算模型所遵循的规则所示，这类功能神经元群落或许可在网络发育过程中，通过遵循基于距离连接的简单约束条件自然形成。