Li Wen-Chang, Cooke Tom, Sautois Bart, Soffe Stephen R, Borisyuk Roman, Roberts Alan
School of Biological Sciences, University of Bristol, Woodland Road, Bristol BS8 1UG, UK.
Neural Dev. 2007 Sep 10;2:17. doi: 10.1186/1749-8104-2-17.
How specific are the synaptic connections formed as neuronal networks develop and can simple rules account for the formation of functioning circuits? These questions are assessed in the spinal circuits controlling swimming in hatchling frog tadpoles. This is possible because detailed information is now available on the identity and synaptic connections of the main types of neuron.
The probabilities of synapses between 7 types of identified spinal neuron were measured directly by making electrical recordings from 500 pairs of neurons. For the same neuron types, the dorso-ventral distributions of axons and dendrites were measured and then used to calculate the probabilities that axons would encounter particular dendrites and so potentially form synaptic connections. Surprisingly, synapses were found between all types of neuron but contact probabilities could be predicted simply by the anatomical overlap of their axons and dendrites. These results suggested that synapse formation may not require axons to recognise specific, correct dendrites. To test the plausibility of simpler hypotheses, we first made computational models that were able to generate longitudinal axon growth paths and reproduce the axon distribution patterns and synaptic contact probabilities found in the spinal cord. To test if probabilistic rules could produce functioning spinal networks, we then made realistic computational models of spinal cord neurons, giving them established cell-specific properties and connecting them into networks using the contact probabilities we had determined. A majority of these networks produced robust swimming activity.
Simple factors such as morphogen gradients controlling dorso-ventral soma, dendrite and axon positions may sufficiently constrain the synaptic connections made between different types of neuron as the spinal cord first develops and allow functional networks to form. Our analysis implies that detailed cellular recognition between spinal neuron types may not be necessary for the reliable formation of functional networks to generate early behaviour like swimming.
随着神经网络的发育，所形成的突触连接有多特异？简单的规则能否解释功能回路的形成？在控制刚孵化出的青蛙蝌蚪游泳的脊髓回路中对这些问题进行了评估。这是可行的，因为现在已经有了关于主要神经元类型的身份和突触连接的详细信息。
通过对500对神经元进行电记录，直接测量了7种已识别的脊髓神经元之间突触形成的概率。对于相同的神经元类型，测量了轴突和树突的背腹分布，然后用于计算轴突遇到特定树突并因此可能形成突触连接的概率。令人惊讶的是，在所有类型的神经元之间都发现了突触，但接触概率可以简单地通过它们的轴突和树突的解剖学重叠来预测。这些结果表明，突触形成可能不需要轴突识别特定的、正确的树突。为了检验更简单假设的合理性，我们首先构建了能够生成纵向轴突生长路径并再现脊髓中发现的轴突分布模式和突触接触概率的计算模型。为了测试概率规则是否能产生功能正常的脊髓网络，我们随后构建了脊髓神经元的真实计算模型，赋予它们既定的细胞特异性特性，并使用我们确定的接触概率将它们连接成网络。这些网络中的大多数产生了强健的游泳活动。
诸如控制背腹体细胞、树突和轴突位置的形态发生素梯度等简单因素，可能在脊髓最初发育时就足以限制不同类型神经元之间形成的突触连接，并允许功能网络的形成。我们的分析表明，对于像游泳这样的早期行为，功能网络的可靠形成可能不需要脊髓神经元类型之间进行详细的细胞识别。
