Speed and segmentation control mechanisms characterized in rhythmically-active circuits created from spinal neurons produced from genetically-tagged embryonic stem cells

速度和分割控制机制,其特征是节律性活动回路,由带有基因标记的胚胎干细胞产生的脊髓神经元产生

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作者:Matthew J Sternfeld, Christopher A Hinckley, Niall J Moore, Matthew T Pankratz, Kathryn L Hilde, Shawn P Driscoll, Marito Hayashi, Neal D Amin, Dario Bonanomi, Wesley D Gifford, Kamal Sharma, Martyn Goulding, Samuel L Pfaff

Abstract

Flexible neural networks, such as the interconnected spinal neurons that control distinct motor actions, can switch their activity to produce different behaviors. Both excitatory (E) and inhibitory (I) spinal neurons are necessary for motor behavior, but the influence of recruiting different ratios of E-to-I cells remains unclear. We constructed synthetic microphysical neural networks, called circuitoids, using precise combinations of spinal neuron subtypes derived from mouse stem cells. Circuitoids of purified excitatory interneurons were sufficient to generate oscillatory bursts with properties similar to in vivo central pattern generators. Inhibitory V1 neurons provided dual layers of regulation within excitatory rhythmogenic networks - they increased the rhythmic burst frequency of excitatory V3 neurons, and segmented excitatory motor neuron activity into sub-networks. Accordingly, the speed and pattern of spinal circuits that underlie complex motor behaviors may be regulated by quantitatively gating the intra-network cellular activity ratio of E-to-I neurons.

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