Juvenile (postnatal day 16) mice lacking Na_v1.6 channels (null-mutant Scn8a^dmu) have reduced photoreceptor function, which is unexpected given that Na_v channels have not been detected in mouse photoreceptors and do not contribute appreciably to photoreceptor function in adults. We demonstrate that acute block of Na_v channels with intravitreal TTX in juvenile (P16) wild-type mice has no effect on photoreceptor function. However, reduced light activity by prolonged dark adaptation from P8 caused significant reduction in photoreceptor function at P16. Injecting TTX into the retrobulbar space at P16 to specifically block Na_v channels in the optic nerve also caused a reduction in photoreceptor function comparable to that seen at P16 in null-mutant Scn8a mice. In both P16 null-mutant Scn8a^dmu and retrobulbar TTX-injected wild-type mice, photoreceptor function was restored following intravitreal injection of the TrkB receptor agonist 7,8-dihydroxyflavone, linking Na_v-dependent retrograde transport to TrkB-dependent neurotrophic factor production pathways as a modulatory influence of photoreceptor function at P16. We also found that in Scn8a^dmu mice, photoreceptor function recovers by P22-25 despite more precarious general health of the animal. Retrobulbar injection of TTX in the wild type still reduced the photoreceptor response at this age but to a lesser extent, suggesting that Na_v-dependent modulation of photoreceptor function is largely transient, peaking soon after eye opening. Together, these results suggest that the general photosensitivity of the retina is modulated following eye opening by retrograde transport through activity-dependent retinal ganglion cell axonal signaling targeting TrkB receptors.

中文翻译：

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小鼠出生后发育过程中电压门控钠通道依赖的轴突后调节光感受器功能

缺乏 Na _v 1.6 通道（无效突变Scn8a ^dmu）的幼年（出生后第 16 天）小鼠的光感受器功能降低，这是出乎意料的，因为在小鼠光感受器中未检测到 Na _v通道并且对成人的光感受器功能没有明显贡献。我们证明在幼年 (P16) 野生型小鼠玻璃体内 TTX急性阻断 Na _{v通道对感光器功能没有影响。}然而，P8 延长暗适应导致的光活性降低导致 P16 的感光器功能显着降低。在 P16 将 TTX 注入球后空间以特异性阻断 Na _v视神经中的通道也导致光感受器功能的降低，与在无效突变Scn8a小鼠中看到的 P16 相当。在 P16 无效突变Scn8a ^dmu和球后 TTX 注射的野生型小鼠中，玻璃体内注射 TrkB 受体激动剂 7,8-二羟基黄酮后，感光器功能恢复，将 Na _v依赖性逆行转运与 TrkB 依赖性神经营养因子产生联系起来通路作为 P16 光感受器功能的调节影响。我们还发现在Scn8a ^dmu小鼠，尽管动物的一般健康状况更加不稳定，但 P22-25 的感光功能恢复。野生型球后注射 TTX 仍会降低这个年龄的感光器反应，但程度较轻，这表明 Na _v依赖的感光器功能调节在很大程度上是短暂的，在睁眼后很快达到峰值。总之，这些结果表明，视网膜的一般光敏性在睁眼后通过逆行运输通过靶向 TrkB 受体的活动依赖性视网膜神经节细胞轴突信号传导进行调节。