Department of Physiology, Yamagata University School of Medicine, Yamagata 990-9585, Japan,
Department of Neuropsychiatry.
J Neurosci. 2019 May 22;39(21):4036-4050. doi: 10.1523/JNEUROSCI.1619-18.2019. Epub 2019 Mar 12.
The axonal conduction of action potentials affects the absolute time it takes to transmit nerve impulses as well as temporal summation at destination synapses. At the physiological level, oligodendrocyte depolarization facilitates axonal conduction along myelinated fibers in the hippocampus; however, the functional significance of this facilitation is largely unknown. In this study, we examined the physiology of the facilitation of axonal conduction by investigating the changes in synaptic responses at destination synapses using male and female mice in which channelrhodopsin-2 expression was restricted to oligodendrocytes. The subiculum, one of the projection areas of the examined axons at the alveus of the hippocampus, is divided into three regions (proximal, mid, and distal) and contains two types of principal neurons: regular firing and bursting pyramidal cells. We found a significant increase in excitatory synaptic responses following optogenetic oligodendrocyte depolarization in bursting neurons at two of the three regions, but not in regular firing neurons at any region. The long-term potentiation (LTP) induced by theta burst stimulation at the synapses showing a significant increase was also enhanced after oligodendrocyte depolarization. Conversely, the reduction of oligodendrocyte depolarization during theta burst stimulation, which was achieved by photostimulation of archaerhodopsin-T expressed selectively on oligodendrocytes, reduced the magnitude of LTP. These results show that oligodendrocyte depolarization contributes to the fine control of synaptic activity between the axons they myelinate and targets subicular cells in a region- and cell type-specific manner, and suggest that oligodendrocyte depolarization during conditioning of stimuli is involved in the induction of LTP. All activity in the nervous system depends on the propagation of action potentials. Changes in the axonal conduction of action potentials influence the timing of synaptic transmission and information processing in neural circuits. At the physiological level, oligodendrocyte depolarization facilitates axonal conduction along myelinated fibers. In this study, we investigated the functional significance of the facilitation of axonal conduction induced by physiological oligodendrocyte depolarization. Using optogenetics and electrophysiological recordings, we demonstrated that oligodendrocyte depolarization in mice expressing channelrhodopsin-2 on oligodendrocytes increased excitatory synaptic responses and enhanced the induction of long-term potentiation at destination synapses in a region- and cell type-specific manner. This facilitation may have a hitherto unappreciated influence on the transfer of information between regions in the nervous system.
动作电位的轴突传导影响神经冲动传递的绝对时间以及目标突触的时间总和。在生理水平上，少突胶质细胞去极化有利于海马髓鞘纤维中的轴突传导；然而，这种促进作用的功能意义在很大程度上是未知的。在这项研究中，我们通过研究使用在少突胶质细胞中表达通道视紫红质-2 的雄性和雌性小鼠中目的地突触处的突触反应变化来检查轴突传导促进的生理学。海马回的齿状回，被检查的轴突的投射区之一，分为三个区域（近端、中间和远端），包含两种主要的神经元类型：规则放电和爆发式锥体神经元。我们发现，在三个区域中的两个区域的爆发式神经元中，光遗传学上的少突胶质细胞去极化后，兴奋性突触反应显著增加，但在任何区域的规则放电神经元中均未增加。在显示显著增加的突触处诱导的长时程增强（LTP）也在少突胶质细胞去极化后增强。相反，通过选择性地在少突胶质细胞上表达的 archaeerhodopsin-T 的光刺激在 theta 爆发刺激期间减少少突胶质细胞去极化，减少了 LTP 的幅度。这些结果表明，少突胶质细胞去极化以区域和细胞类型特异性的方式有助于调节它们髓鞘化的轴突与目标齿状回细胞之间的突触活动，并表明刺激条件下的少突胶质细胞去极化参与了 LTP 的诱导。神经系统中的所有活动都依赖于动作电位的传播。动作电位的轴突传导的变化影响神经回路中突触传递和信息处理的时间。在生理水平上，少突胶质细胞去极化有利于髓鞘纤维中的轴突传导。在这项研究中，我们研究了生理少突胶质细胞去极化诱导的轴突传导促进的功能意义。使用光遗传学和电生理记录，我们证明了在表达通道视紫红质-2 的少突胶质细胞的小鼠中，少突胶质细胞去极化以区域和细胞类型特异性的方式增加了兴奋性突触反应，并增强了目的地突触的长时程增强的诱导。这种促进作用可能对神经系统中区域之间的信息传递产生了迄今为止未被认识到的影响。
