Institute of Systems Neuroscience, National Tsing Hua University, Hsinchu 30013, Taiwan.
Institute of Systems Neuroscience, National Tsing Hua University, Hsinchu 30013, Taiwan
eNeuro. 2019 Aug 9;6(4). doi: 10.1523/ENEURO.0391-18.2019. Print 2019 Jul/Aug.
Neurons in the adult mammalian CNS fails to regenerate after severe injury. However, it is known that an increase in neural activity occurs in mouse retinal ganglion cells (RGCs) after extrinsic stimulation and this can induce axon growth. In the present study, we applied an optogenetic approach using a mouse model, specifically involving channelrhodopsin-2 (ChR2) expression in RGCs. We investigated whether modulation of RGC neural activity exclusively by blue light stimulation is able to promote neurite outgrowth of postnatal retinal explants. The results showed that activation of RGCs expressing ChR2 by 20 Hz blue light for 1 h is a most effective way of enhancing neurite outgrowth in postnatal retinas. This is achieved via gap junctions that spread neural activity across the whole retina. Moreover, we found that activation of intrinsic photosensitive RGCs (ipRGCs) by blue light also contributes significantly to the promotion of neurite outgrowth in the same postnatal retinal explants. Our findings not only demonstrate that a short-term increase in RGC neural activity is sufficient to facilitate the neurite outgrowth of retinal explants, but also highlight the fact that the temporal pattern of neural activity in RGCs is a critical factor in regulating axon regeneration.
成年哺乳动物中枢神经系统中的神经元在严重损伤后无法再生。然而，已知在外部刺激后，小鼠视网膜神经节细胞 (RGC) 中的神经活动会增加，这可以诱导轴突生长。在本研究中，我们使用小鼠模型应用了一种光遗传学方法，特别是在 RGC 中表达通道型视紫红质 2 (ChR2)。我们研究了仅通过蓝光刺激来调节 RGC 神经活动是否能够促进出生后视网膜外植体的神经突生长。结果表明，用 20 Hz 蓝光激活表达 ChR2 的 RGC 1 小时是增强出生后视网膜神经突生长的最有效方法。这是通过缝隙连接实现的，缝隙连接将神经活动传播到整个视网膜。此外，我们发现蓝光对内在光敏性 RGCs (ipRGCs) 的激活也显著促进了相同出生后视网膜外植体中神经突的生长。我们的研究结果不仅表明 RGC 神经活动的短期增加足以促进视网膜外植体的神经突生长，还强调了 RGC 中神经活动的时间模式是调节轴突再生的关键因素。
