光曝露はレトログラード性メラノプシン・ドーパミンシグナル伝達を介して網膜波の長期的な可塑性を誘発する

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 micro-electrode array (MEA) recordings from both male and female mice, we demonstrated that prolong light exposure reduces the inter-wave interval and coupling distance of Stage II retinal waves, which can persist for at least 1 hour after light exposure. Notably, these light-induced effects on cholinergic waves were impaired in melanopsin knock-out (MKO) 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 (smFISH), we identified high expression of D2-like receptors, particularly D4R, in the ganglion cell layer (GCL) 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 II 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.Significance statement The formation of complex neuronal circuitry during development is regulated by a combination of intrinsic and extrinsic factors. While the importance of experience-independent processes, such as spontaneous retinal waves, in sensory system maturation is well-established, the circuitry and mechanism of internal and external factors convergence remains poorly understood. In this study, we demonstrate that light exposure modulates the properties of Stage II retinal waves through the ipRGC-dopamine retrograde signaling pathway. Our findings reveal a critical convergence pathway between ipRGC and spontaneous retinal waves. This highlights how environmental cues, such as light, interact with intrinsic developmental programs to shape the assembly of mature visual system circuitry, indicating the importance of early light exposure during development.