Kobayashi Ryota, Nishimaru Hiroshi, Nishijo Hisao
Principles of Informatics Research Division, National Institute of Informatics, 2-1-2 Hitotsubashi, Chiyoda-ku, Tokyo 101-0003, Japan; Department of Informatics, SOKENDAI (The Graduate University for Advanced Studies), 2-1-2 Hitotsubashi, Chiyoda-ku, Tokyo, Japan.
System Emotional Science, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan; Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan.
Neuroscience. 2016 Oct 29;335:72-81. doi: 10.1016/j.neuroscience.2016.08.027. Epub 2016 Aug 22.
The rhythmic activity of motoneurons (MNs) that underlies locomotion in mammals is generated by synaptic inputs from the locomotor network in the spinal cord. Thus, the quantitative estimation of excitatory and inhibitory synaptic conductances is essential to understand the mechanism by which the network generates the functional motor output. Conductance estimation is obtained from the voltage-current relationship measured by voltage-clamp- or current-clamp-recording with knowledge of the leak parameters of the recorded neuron. However, it is often difficult to obtain sufficient data to estimate synaptic conductances due to technical difficulties in electrophysiological experiments using in vivo or in vitro preparations. To address this problem, we estimated the average variations in excitatory and inhibitory synaptic conductance during a locomotion cycle from a single voltage trace without measuring the leak parameters. We found that the conductance variations can be accurately reconstructed from a voltage trace of 10 cycles by analyzing synthetic data generated from a computational model. Next, the conductance variations were estimated from mouse spinal MNs in vitro during drug-induced-locomotor-like activity. We found that the peak of excitatory conductance occurred during the depolarizing phase of the locomotor cycle, whereas the peak of inhibitory conductance occurred during the hyperpolarizing phase. These results suggest that the locomotor-like activity is generated by push-pull modulation via excitatory and inhibitory synaptic inputs.
哺乳动物运动所依赖的运动神经元(MNs)的节律性活动是由脊髓中运动网络的突触输入产生的。因此,定量估计兴奋性和抑制性突触电导对于理解该网络产生功能性运动输出的机制至关重要。电导估计是通过电压钳或电流钳记录测量的电压-电流关系,并结合所记录神经元的泄漏参数知识获得的。然而,由于在使用体内或体外制备的电生理实验中存在技术困难,往往难以获得足够的数据来估计突触电导。为了解决这个问题,我们从单个电压轨迹估计了运动周期内兴奋性和抑制性突触电导的平均变化,而无需测量泄漏参数。我们发现,通过分析由计算模型生成的合成数据,可以从10个周期的电压轨迹准确重建电导变化。接下来,在体外对小鼠脊髓MNs在药物诱导的类似运动活动期间的电导变化进行了估计。我们发现,兴奋性电导的峰值出现在运动周期的去极化阶段,而抑制性电导的峰值出现在超极化阶段。这些结果表明,类似运动的活动是由兴奋性和抑制性突触输入的推挽调制产生的。