Arc Regulates Experience-Dependent Persistent Firing Patterns in Frontal Cortex
Arc Regulates Experience-Dependent Persistent Firing Patterns in Frontal Cortex
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DOI：
10.1523/jneurosci.0167-14.2014
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发表时间：
2014-05-07
影响因子：
5.3
通讯作者：
Wang, Kuan Hong
中科院分区：
文献类型：
--
作者：
Ren, Ming;Cao, Vania;Wang, Kuan Hong
大脑将过去的经验信息编码到特定的神经元群体中，这些神经元通过激发动作电位相互交流。经验依赖性神经可塑性的研究主要集中在响应神经元输入的个体突触变化。指示的神经元输出传输到下游神经元，持续放电模式的影响，在选择性神经元群体的先前经验。然而，很少有人知道的分子和细胞的机制，经验相关的持续放电模式的调节在特定的神经元群体。使用额叶皮层切片制备的转基因小鼠携带荧光报告弧基因表达，本研究探讨了行为经验和活动调节弧基因的影响模式的神经元放电。我们发现运动训练增加了兴奋性神经元亚群中Arc的表达。这些神经元表现出持续放电，与来自相同小鼠的ARC阴性神经元或来自未经训练小鼠的神经元形成对比。此外，在携带Arc基因缺失的小鼠中，额叶皮层回路仍然存在，以启动经验依赖性基因表达，但此后持续放电的水平降低。最后，我们的研究结果表明，持续活动的出现与NMDA型谷氨酸受体功能的ARC依赖性变化有关，而不是AMPA型受体或膜兴奋性的变化。因此，我们的研究结果揭示了一个弧依赖的分子途径，通过该途径，基因经验相互作用调节特定神经元群体中持续放电模式的出现。
The brain encodes information about past experience in specific populations of neurons that communicate with one another by firing action potentials. Studies of experience-dependent neural plasticity have largely focused on individual synaptic changes in response to neuronal input. Indicative of the neuronal output transmitted to downstream neurons, persistent firing patterns are affected by prior experience in selective neuronal populations. However, little is known about the molecular and cellular mechanisms by which experience-related persistent firing patterns are regulated in specific neuronal populations. Using frontal cortical slices prepared from transgenic mice carrying a fluorescent reporter of Arc gene expression, this study investigates how behavioral experience and the activity-regulated Arc gene affect patterns of neuronal firing. We found that motor training increases Arc expression in subsets of excitatory neurons. Those neurons exhibit persistent firing in contrast to Arc-negative neurons from the same mice or neurons from the untrained mice. Furthermore, in mice carrying genetic deletion of Arc, the frontal cortical circuitry is still in place to initiate experience-dependent gene expression, but the level of persistent firing thereafter is diminished. Finally, our results showed that the emergence of persistent activity is associated with Arc-dependent changes in the function of NMDA-type glutamate receptors, rather than changes in AMPA-type receptors or membrane excitability. Our findings therefore reveal an Arc-dependent molecular pathway by which geneexperience interaction regulates the emergence of persistent firing patterns in specific neuronal populations.