Department of Mathematics, Humboldt State University, Arcata, California, United States of America.
PLoS One. 2012;7(5):e37292. doi: 10.1371/journal.pone.0037292. Epub 2012 May 18.
Mapping the detailed connectivity patterns (connectomes) of neural circuits is a central goal of neuroscience. The best quantitative approach to analyzing connectome data is still unclear but graph theory has been used with success. We present a graph theoretical model of the posterior lateral line sensorimotor pathway in zebrafish. The model includes 2,616 neurons and 167,114 synaptic connections. Model neurons represent known cell types in zebrafish larvae, and connections were set stochastically following rules based on biological literature. Thus, our model is a uniquely detailed computational representation of a vertebrate connectome. The connectome has low overall connection density, with 2.45% of all possible connections, a value within the physiological range. We used graph theoretical tools to compare the zebrafish connectome graph to small-world, random and structured random graphs of the same size. For each type of graph, 100 randomly generated instantiations were considered. Degree distribution (the number of connections per neuron) varied more in the zebrafish graph than in same size graphs with less biological detail. There was high local clustering and a short average path length between nodes, implying a small-world structure similar to other neural connectomes and complex networks. The graph was found not to be scale-free, in agreement with some other neural connectomes. An experimental lesion was performed that targeted three model brain neurons, including the Mauthner neuron, known to control fast escape turns. The lesion decreased the number of short paths between sensory and motor neurons analogous to the behavioral effects of the same lesion in zebrafish. This model is expandable and can be used to organize and interpret a growing database of information on the zebrafish connectome.
绘制神经回路的详细连接模式(连接组)是神经科学的一个核心目标。分析连接组数据的最佳定量方法尚不清楚,但图论已成功应用。我们提出了斑马鱼后外侧线感觉运动通路的图论模型。该模型包含 2616 个神经元和 167114 个突触连接。模型神经元代表斑马鱼幼虫中的已知细胞类型,连接是根据生物文献中的规则随机设置的。因此,我们的模型是脊椎动物连接组的独特详细计算表示。连接组的整体连接密度低,只有所有可能连接的 2.45%,这是生理范围内的值。我们使用图论工具将斑马鱼连接组图与具有相同大小的小世界、随机和结构随机图进行比较。对于每种类型的图,考虑了 100 个随机生成的实例。与具有较少生物学细节的相同大小的图相比,斑马鱼图中的神经元连接数(每个神经元的连接数)变化更大。节点之间存在高度的局部聚类和短平均路径长度,这意味着具有类似于其他神经连接组和复杂网络的小世界结构。该图被发现不是无标度的,这与其他一些神经连接组一致。进行了针对三个模型脑神经元的实验性损伤,包括控制快速逃避转弯的麦氏神经元。损伤减少了感觉神经元和运动神经元之间的短路径数量,类似于相同损伤在斑马鱼中的行为效应。该模型可扩展,并可用于组织和解释不断增长的斑马鱼连接组信息数据库。