Spinal Hb9::Cre-derived excitatory interneurons contribute to rhythm generation in the mouse.
Spinal Hb9::Cre-derived excitatory interneurons contribute to rhythm generation in the mouse.
复制标题
脊柱HB9 :: Cre衍生的兴奋性中间神经元在小鼠中产生节奏。
DOI：
10.1038/srep41369
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发表时间：
2017-01-27
影响因子：
4.6
通讯作者：
Kiehn O
中科院分区：
文献类型：
--
作者：
Caldeira V;Dougherty KJ;Borgius L;Kiehn O
节律产生神经元被认为是胸腰段哺乳动物脊髓中同侧投射的兴奋性神经元。最近，Shox2中间神经元的一个子集（Shox2非v2a INs）被发现满足这些标准，并构成了节律产生群体的一小部分。在这里，我们使用Hb9::Cre小鼠对Hb9::Cre衍生的兴奋性中间神经元（INs）进行遗传操作，以确定这些INs在节律产生中的作用。我们证明，这条线捕获了一致的脊髓INs群体，这些INs在神经递质表型和祖细胞结构域方面是混合的，但不与Shox2非v2a群体重叠。我们还表明，Hb9:: cre衍生的INs包括相对较小的在出生后继续表达Hb9的INs的医学人群。当通过从Hb9:: cre衍生的INs中删除Vglut2选择性阻断兴奋性神经传递时，这些索和对照之间的左右和/或屈伸肌相位没有差异，这表明兴奋性Hb9:: cre衍生的INs不影响模式的产生。相比之下，Hb9::Cre-Vglut2Δ/Δ小鼠的脊髓运动活动频率明显低于对照组。总的来说，我们的研究结果表明，兴奋性Hb9:: cre衍生的INs构成了一个独特的神经元群，参与了脊柱运动的节律产生核心。
Rhythm generating neurons are thought to be ipsilaterally-projecting excitatory neurons in the thoracolumbar mammalian spinal cord. Recently, a subset of Shox2 interneurons (Shox2 non-V2a INs) was found to fulfill these criteria and make up a fraction of the rhythm-generating population. Here we use Hb9::Cre mice to genetically manipulate Hb9::Cre-derived excitatory interneurons (INs) in order to determine the role of these INs in rhythm generation. We demonstrate that this line captures a consistent population of spinal INs which is mixed with respect to neurotransmitter phenotype and progenitor domain, but does not overlap with the Shox2 non-V2a population. We also show that Hb9::Cre-derived INs include the comparatively small medial population of INs which continues to express Hb9 postnatally. When excitatory neurotransmission is selectively blocked by deleting Vglut2 from Hb9::Cre-derived INs, there is no difference in left-right and/or flexor-extensor phasing between these cords and controls, suggesting that excitatory Hb9::Cre-derived INs do not affect pattern generation. In contrast, the frequencies of locomotor activity are significantly lower in cords from Hb9::Cre-Vglut2Δ/Δ mice than in cords from controls. Collectively, our findings indicate that excitatory Hb9::Cre-derived INs constitute a distinct population of neurons that participates in the rhythm generating kernel for spinal locomotion.