Flood Michael D, Moore-Dotson Johnnie M, Eggers Erika D
Departments of Physiology and Biomedical Engineering, University of Arizona , Tucson, Arizona.
J Neurophysiol. 2018 Aug 1;120(2):867-879. doi: 10.1152/jn.00855.2017. Epub 2018 May 30.
Dopamine modulation of retinal signaling has been shown to be an important part of retinal adaptation to increased background light levels, but the role of dopamine modulation of retinal inhibition is not clear. We previously showed that light adaptation causes a large reduction in inhibition to rod bipolar cells, potentially to match the decrease in excitation after rod saturation. In this study, we determined how dopamine D1 receptors in the inner retina contribute to this modulation. We found that D1 receptor activation significantly decreased the magnitude of inhibitory light responses from rod bipolar cells, whereas D1 receptor blockade during light adaptation partially prevented this decline. To determine what mechanisms were involved in the modulation of inhibitory light responses, we measured the effect of D1 receptor activation on spontaneous currents and currents evoked from electrically stimulating amacrine cell inputs to rod bipolar cells. D1 receptor activation decreased the frequency of spontaneous inhibition with no change in event amplitudes, suggesting a presynaptic change in amacrine cell activity in agreement with previous reports that rod bipolar cells lack D1 receptors. Additionally, we found that D1 receptor activation reduced the amplitude of electrically evoked responses, showing that D1 receptors can modulate amacrine cells directly. Our results suggest that D1 receptor activation can replicate a large portion but not all of the effects of light adaptation, likely by modulating release from amacrine cells onto rod bipolar cells. NEW & NOTEWORTHY We demonstrated a new aspect of dopaminergic signaling that is involved in mediating light adaptation of retinal inhibition. This D1 receptor-dependent mechanism likely acts through receptors located directly on amacrine cells, in addition to its potential role in modulating the strength of serial inhibition between amacrine cells. Our results also suggest that another D2/D4 receptor-dependent or dopamine-independent mechanism must also be involved in light adaptation of inhibition to rod bipolar cells.
多巴胺对视网膜信号的调节已被证明是视网膜适应背景光水平升高的重要组成部分,但多巴胺对视网膜抑制的调节作用尚不清楚。我们之前表明,光适应会导致对视杆双极细胞的抑制大幅减少,这可能是为了与视杆饱和后兴奋性的降低相匹配。在本研究中,我们确定了视网膜内层的多巴胺D1受体如何促成这种调节。我们发现,D1受体激活显著降低了视杆双极细胞的抑制性光反应幅度,而在光适应期间阻断D1受体则部分阻止了这种下降。为了确定抑制性光反应调节涉及哪些机制,我们测量了D1受体激活对自发电流以及电刺激无长突细胞输入到视杆双极细胞所诱发电流的影响。D1受体激活降低了自发抑制的频率,而事件幅度没有变化,这表明无长突细胞活性发生了突触前变化,这与之前关于视杆双极细胞缺乏D1受体的报道一致。此外,我们发现D1受体激活降低了电诱发反应的幅度,表明D1受体可以直接调节无长突细胞。我们的结果表明,D1受体激活可以复制光适应的大部分但不是全部效应,可能是通过调节无长突细胞对视杆双极细胞的释放来实现。新发现与值得注意之处我们证明了多巴胺能信号传导的一个新方面,它参与介导视网膜抑制的光适应。这种依赖D1受体的机制可能通过直接位于无长突细胞上的受体起作用,此外它还可能在调节无长突细胞之间的串行抑制强度方面发挥作用。我们的结果还表明,另一种依赖D2/D4受体或不依赖多巴胺的机制也必定参与对视杆双极细胞抑制的光适应。