Gene networks activated by specific patterns of action potentials in dorsal root ganglia neurons.
Gene networks activated by specific patterns of action potentials in dorsal root ganglia neurons.
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DOI：
10.1038/srep43765
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发表时间：
2017-03-03
影响因子：
4.6
通讯作者：
Fields RD
中科院分区：
文献类型：
--
作者：
Lee PR;Cohen JE;Iacobas DA;Iacobas S;Fields RD
基因调控网络是细胞规格、突触连接生长和适应的长期变化的基础，这些变化发生在整个新生儿和出生后的生命中。在这里，我们表明神经元的转录反应对动作电位放电模式的时间性质非常敏感。用相同数量的动作电位刺激神经元，但间隔时间不同。我们发现，通过激活或抑制不同的转录网络，这些动作电位放电时间的细微变化对数百个基因进行了不同的调节，这些基因跨越了许多功能类别。我们的研究结果表明，神经元对环境刺激的转录反应，编码为动作电位放电模式，可能对动作电位传递的时间性质非常敏感，而不是刺激强度或传递的动作电位总数。这些数据表明，动作电位放电的时间动力学是调节细胞内信号通路和神经元细胞外信号基因表达的关键因素。
Gene regulatory networks underlie the long-term changes in cell specification, growth of synaptic connections, and adaptation that occur throughout neonatal and postnatal life. Here we show that the transcriptional response in neurons is exquisitely sensitive to the temporal nature of action potential firing patterns. Neurons were electrically stimulated with the same number of action potentials, but with different inter-burst intervals. We found that these subtle alterations in the timing of action potential firing differentially regulates hundreds of genes, across many functional categories, through the activation or repression of distinct transcriptional networks. Our results demonstrate that the transcriptional response in neurons to environmental stimuli, coded in the pattern of action potential firing, can be very sensitive to the temporal nature of action potential delivery rather than the intensity of stimulation or the total number of action potentials delivered. These data identify temporal kinetics of action potential firing as critical components regulating intracellular signalling pathways and gene expression in neurons to extracellular cues during early development and throughout life.