EphA4 defines a class of excitatory locomotor-related interneurons

EphA4 defines a class of excitatory locomotor-related interneurons
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DOI:
10.1073/pnas.0503317102
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发表时间:
2005-09-27
影响因子:
11.1
通讯作者:
Kiehn, O
Kiehn, O
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Butt, SJB;Lundfald, L;Kiehn, O

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相对而言,我们对构成哺乳动物运动中枢模式发生器的中间神经元以及它们如何相互作用产生行为知之甚少。一个潜在的研究途径是确定对中间神经元群体特异的遗传标记,这将有助于进一步探索这些细胞在网络中的作用。一种这样的标志物是EphA4轴突导向受体。EphA4缺失小鼠显示出异常的兔样跳跃步态,这被认为是正常交替的双侧运动网络通过异常交叉连接同步化的结果。在这项研究中,我们进行了全细胞膜片钳EphA4阳性的中间神经元的屈肌区(L2)的运动网络。我们提供的证据表明,虽然EphA4阳性中间神经元并不完全是一个同质的人口,他们中的大多数火灾的节奏。此外,这些中间神经元的一个子集提供直接兴奋同侧运动神经元确定的尖峰触发平均的本地腹根直流跟踪。我们的研究结果证实了EphA4阳性中间神经元作为同侧运动网络的重要组成部分的作用,并描述了一组假定的兴奋性中枢模式发生器神经元。
Relatively little is known about the interneurons that constitute the mammalian locomotor central pattern generator and how they interact to produce behavior. A potential avenue of research is to identify genetic markers specific to interneuron populations that will assist further exploration of the role of these cells in the network. One such marker is the EphA4 axon guidance receptor. EphA4-null mice display an abnormal rabbit-like hopping gait that is thought to be the result of synchronization of the normally alternating, bilateral locomotor network via aberrant crossed connections. In this study, we have performed whole-cell patch clamp on EphA4-positive interneurons in the flexor region (L2) of the locomotor network. We provide evidence that although EphA4 positive interneurons are not entirely a homogeneous population, most of them fire in a rhythmic manner. Moreover, a subset of these interneurons provide direct excitation to ipsilateral motor neurons as determined by spike-triggered averaging of the local ventral root DC trace. Our findings substantiate the role of EphA4-positive interneurons as significant components of the ipsilateral locomotor network and describe a group of putative excitatory central pattern generator neurons.