Prolonged Light Exposure Induces Long-Lasting Retinal Wave Plasticity via Retrograde Melanopsin-Dopamine Signaling.

The spontaneous activity in the developing retina is necessary for the maturation of the neuronal circuitry in visual-associated brain areas. While previous studies have shown that the activation of intrinsically photosensitive retinal ganglion cells (ipRGCs) contributes to visual development, its effects and mechanisms remain largely unclear. Here, using microelectrode array recordings from both male and female mice, we demonstrated that prolong light exposure reduces the interwave interval and coupling distance of Stage 2 retinal waves, which can persist for at least 1 h after light exposure. Notably, these light-induced effects on cholinergic waves were impaired in melanopsin knock-out mice. Additionally, the light-induced retinal wave modulation is mediated by the dopaminergic pathway, primarily through D4 receptors. Using single-molecule fluorescence in situ hybridization, we identified high expression of D2-like receptors, particularly D4R, in the ganglion cell layer and ON-type starburst amacrine cells (SACs) during early postnatal development. Furthermore, we found that gap junction coupling in SACs was increased after light exposure, which can be blocked by D2-like receptor antagonists. Overall, our study reveals that the key properties of spontaneous Stage 2 retinal waves can be regulated by environmental light through ipRGCs. This regulation involves dopaminergic signaling, highlighting the critical role of ipRGC in retinal wave modulation and the convergence of experience-dependent and independent circuitry refinement processes.