Light-induced extrasynaptic dopamine release in the retina reduces adenosine 3′,5′-cyclic monophosphate (cAMP) in rod photoreceptor cells, which is thought to mediate light-dependent desensitization. However, the fine time course of the cAMP dynamics in rods remains elusive due to technical difficulty. Here, we visualized the spatiotemporal regulation of cAMP-dependent protein kinase (PKA) in mouse rods by two-photon live imaging of retinal explants of PKAchu mice, which express a fluorescent biosensor for PKA. Unexpectedly, in addition to the light-on-induced suppression, we observed prominent light-off-induced PKA activation. This activation required photopic light intensity and was confined to the illuminated rods. The estimated maximum spectral sensitivity of 489 nm and loss of the light-off-induced PKA activation in rod-transducin-knockout retinas strongly suggest the involvement of rhodopsin. In support of this notion, rhodopsin-deficient retinal explants showed only the light-on-induced PKA suppression. Taken together, these results suggest that, upon photopic light stimulation, rhodopsin and dopamine signals are integrated to shape the light-off-induced cAMP production and following PKA activation. This may support the dark adaptation of rods.

光诱导的突触外多巴胺在视网膜中的释放减少了杆状感光细胞中的腺苷3'，5'-环一磷酸（cAMP），据认为可介导光依赖性脱敏。然而，由于技术上的困难，棒中cAMP动力学的精细时间过程仍然难以捉摸。在这里，我们通过对PKAchu小鼠的视网膜外植体进行双光子实时成像，对小鼠棒中cAMP依赖性蛋白激酶（PKA）的时空调节进行了可视化，该表达表达了PKA荧光生物传感器。出乎意料的是，除了起光诱导的抑制作用外，我们还观察到了显着的起光诱导的PKA激活。该激活需要可见光强度，并且仅限于照明棒。估计的最大光谱灵敏度为489 nm，并且在视杆转导蛋白敲除视网膜中起燃诱导的PKA激活的丧失强烈提示视紫红质的参与。为了支持这一观点，视紫红质缺乏的视网膜外植体仅显示了光诱导的PKA抑制。两者合计，这些结果表明，在视光刺激下，视紫红质和多巴胺信号被整合以形成起燃诱导的cAMP产生并在PKA激活之后。这可以支持杆的暗适应。视紫红质和多巴胺信号被整合以塑造起燃诱导的cAMP产生以及PKA激活。这可以支持杆的暗适应。视紫红质和多巴胺信号被整合以塑造起燃诱导的cAMP产生以及PKA激活。这可以支持杆的暗适应。