Bergum Nikolas, Berezin Casey-Tyler, Vigh Jozsef
Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado, United States.
Cell and Molecular Biology Graduate Program, Colorado State University, Fort Collins,Colorado, United States.
J Neurophysiol. 2024 Aug 1;132(2):501-513. doi: 10.1152/jn.00457.2023. Epub 2024 Jul 3.
Neuromodulation in the retina is crucial for effective processing of retinal signal at different levels of illuminance. Intrinsically photosensitive retinal ganglion cells (ipRGCs), the neurons that drive nonimage-forming visual functions, express a variety of neuromodulatory receptors that tune intrinsic excitability as well as synaptic inputs. Past research has examined actions of neuromodulators on light responsiveness of ipRGCs, but less is known about how neuromodulation affects synaptic currents in ipRGCs. To better understand how neuromodulators affect synaptic processing in ipRGC, we examine actions of opioid and dopamine agonists have on inhibitory synaptic currents in ipRGCs. Although µ-opioid receptor (MOR) activation had no effect on γ-aminobutyric acid (GABA) currents, dopamine [via the D1-type dopamine receptor (D1R)]) amplified GABAergic currents in a subset of ipRGCs. Furthermore, this D1R-mediated facilitation of the GABA conductance in ipRGCs was mediated by a cAMP/PKA-dependent mechanism. Taken together, these findings reinforce the idea that dopamine's modulatory role in retinal adaptation affects both nonimage-forming and image-forming visual functions. Neuromodulators such as dopamine are important regulators of retinal function. Here, we demonstrate that dopamine increases inhibitory inputs to intrinsically photosensitive retinal ganglion cells (ipRGCs), in addition to its previously established effect on intrinsic light responsiveness. This indicates that dopamine, in addition to its ability to intrinsically modulate ipRGC activity, can also affect synaptic inputs to ipRGCs, thereby tuning retina circuits involved in nonimage-forming visual functions.
视网膜中的神经调节对于在不同光照水平下有效处理视网膜信号至关重要。内在光敏性视网膜神经节细胞（ipRGCs）是驱动非成像视觉功能的神经元，它们表达多种神经调节受体，这些受体可调节内在兴奋性以及突触输入。过去的研究已经考察了神经调质对ipRGCs光反应性的作用，但对于神经调节如何影响ipRGCs中的突触电流却知之甚少。为了更好地理解神经调质如何影响ipRGCs中的突触处理，我们研究了阿片类药物和多巴胺激动剂对ipRGCs中抑制性突触电流的作用。虽然μ-阿片受体（MOR）的激活对γ-氨基丁酸（GABA）电流没有影响，但多巴胺[通过D1型多巴胺受体（D1R）]在一部分ipRGCs中增强了GABA能电流。此外，这种D1R介导的ipRGCs中GABA电导的促进作用是由一种cAMP/PKA依赖性机制介导的。综上所述，这些发现强化了多巴胺在视网膜适应中的调节作用影响非成像和成像视觉功能这一观点。多巴胺等神经调质是视网膜功能的重要调节因子。在这里，我们证明多巴胺除了其先前确定的对内在光反应性的影响外，还增加了对内在光敏性视网膜神经节细胞（ipRGCs）的抑制性输入。这表明多巴胺除了具有内在调节ipRGCs活动的能力外，还可以影响ipRGCs的突触输入，从而调节参与非成像视觉功能的视网膜回路。
