Arroyo David A, Kirkby Lowry A, Feller Marla B
Department of Molecular and Cell Biology.
Biophysics Graduate Group, and.
J Neurosci. 2016 Jun 29;36(26):6892-905. doi: 10.1523/JNEUROSCI.0572-16.2016.
Before the maturation of rod and cone photoreceptors, the developing retina relies on light detection by intrinsically photosensitive retinal ganglion cells (ipRGCs) to drive early light-dependent behaviors. ipRGCs are output neurons of the retina; however, they also form functional microcircuits within the retina itself. Whether ipRGC microcircuits exist during development and whether they influence early light detection remain unknown. Here, we investigate the neural circuit that underlies the ipRGC-driven light response in developing mice. We use a combination of calcium imaging, tracer coupling, and electrophysiology experiments to show that ipRGCs form extensive gap junction networks that strongly contribute to the overall light response of the developing retina. Interestingly, we found that gap junction coupling was modulated by spontaneous retinal waves, such that acute blockade of waves dramatically increased the extent of coupling and hence increased the number of light-responsive neurons. Moreover, using an optical sensor, we found that this wave-dependent modulation of coupling is driven by dopamine that is phasically released by retinal waves. Our results demonstrate that ipRGCs form gap junction microcircuits during development that are modulated by retinal waves; these circuits determine the extent of the light response and thus potentially impact the processing of early visual information and light-dependent developmental functions.
Light-dependent functions in early development are mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs). Here we show that ipRGCs form an extensive gap junction network with other retinal neurons, including other ipRGCs, which shapes the retina's overall light response. Blocking cholinergic retinal waves, which are the primary source of neural activity before maturation of photoreceptors, increased the extent of ipRGC gap junction networks, thus increasing the number of light-responsive cells. We determined that this modulation of ipRGC gap junction networks occurs via dopamine released by waves. These results demonstrate that retinal waves mediate dopaminergic modulation of gap junction networks to regulate pre-vision light responses.
在视杆和视锥光感受器成熟之前，发育中的视网膜依靠内在光敏性视网膜神经节细胞（ipRGCs）进行光检测，以驱动早期光依赖性行为。ipRGCs是视网膜的输出神经元；然而，它们也在视网膜自身内部形成功能性微电路。ipRGC微电路在发育过程中是否存在以及它们是否影响早期光检测仍不清楚。在这里，我们研究了发育中小鼠中ipRGC驱动的光反应背后的神经回路。我们结合使用钙成像、示踪剂偶联和电生理实验，以表明ipRGCs形成广泛的缝隙连接网络，这对发育中视网膜的整体光反应有很大贡献。有趣的是，我们发现缝隙连接偶联受视网膜自发波调节，以至于急性阻断波会显著增加偶联程度，从而增加光反应神经元的数量。此外，使用光学传感器，我们发现这种波依赖的偶联调节是由视网膜波阶段性释放的多巴胺驱动的。我们的结果表明，ipRGCs在发育过程中形成受视网膜波调节的缝隙连接微电路；这些电路决定光反应的程度，从而可能影响早期视觉信息的处理和光依赖的发育功能。
早期发育中的光依赖性功能由内在光敏性视网膜神经节细胞（ipRGCs）介导。在这里我们表明，ipRGCs与其他视网膜神经元，包括其他ipRGCs，形成广泛的缝隙连接网络，这塑造了视网膜的整体光反应。阻断胆碱能视网膜波，这是光感受器成熟之前神经活动的主要来源，增加了ipRGC缝隙连接网络的程度，从而增加了光反应细胞的数量。我们确定这种ipRGC缝隙连接网络的调节是通过波释放的多巴胺发生的。这些结果表明，视网膜波介导缝隙连接网络的多巴胺能调节，以调节视觉前的光反应。
