体外培养神经元网络功能结构的长时间发育变化

神经功能结构的建立和维持是学习与记忆等高级功能的基础. 因神经网络的结构错综复杂, 节点行为多变且受多种因素的影响, 目前其拓扑结构的形成和维持机制尚不清楚. 基于多电极阵列系统, 本研究连续记录了体外长时间培养的海马神经元网络的自发放电活动; 利用不同电极放电序列之间的互相关系数映射功能连接强度, 构建网络拓扑结构图, 分析其发育特性. 对培养1~18周的3个样本的分析结果显示, 网络拓扑结构的形成和维持具有自组织和自解离特性: 网络连接建立期(1~3周), 邻近节点之间建立连接, 形成局域微网络; 随着网络的发育, 逐步形成多节点的复杂功能结构; 发育成熟期(12周后), 功能连接开始消退, 部分节点脱离网络, 网络聚集程度增加. 不同发育时期网络各节点连接强度的分布均符合幂率分布, 表明无外界输入的培养神经元网络是具有无尺度特征的复杂网络. 本研究有助于复杂神经网络结构的形成及维持机制分析, 为研究神经发育和神经系统信息处理机制提供新的视野.

Long-term characterization of functional structure of cultured hippocampal neuronal networks

One way to understand brain function is to understand how functional structure of neurons organized during development. The underlying mechanism remains unclear because the network topology was too complex. With multi-electrode array system, the spontaneous activity of cultured hippocampal networks was recorded from 1–18 weeks in vitro. We mapped functional networks using cross correlation between pairs of electrodes. Analysis of three cultures indicated self organization and disorganization of cultured networks during long term development. Adjacent neurons in culture began establishing functional connections during 1–3 weeks in vitro. Then, more connections emerged and organized as complex networks. Finally, the network topology became more compact when some connections disappeared after 12 weeks. As the distribution of connections followed a power law during development, the cultured networks showed the characteristic of scale-free network. These works could shed new light on both neural coding and organization mechanisms of nervous system.