Prolonged visual experience accelerates developmental synaptic downscaling via epigenetic regulation and Rab5c mediated AMPA receptor trafficking.

Environmental light significantly influences neural development, yet the specific mechanisms underlying the effects of prolonged visual experience on homeostatic synaptic scaling remain unclear. Using manipulated ambient light conditions, we observed reduced mEPSC amplitudes and visually evoked responses in 20 hr light/4 hr dark (20LE) compared to a standard 12 hr light/12 hr dark (12LE) reared Xenopus laevis tadpoles. Prolonged light exposure accelerates the developmental decline of glutamatergic synaptic transmission via Rab5c-dependent endocytosis of AMPA receptor (AMPAR) subunits GluA1 and GluA2. The synaptic changes were accompanied by increased intrinsic neuronal excitability, but unchanged presynaptic release probability, and coincided with altered dendritic architecture. Notably, synaptic transmission and AMPAR expression were reversible upon re-exposure to standard 12LE conditions. Class I HDAC-mediated histone acetylation links epigenetic regulation to sustained AMPAR downregulation, revealing a two-stage process in which prolonged visual experience drives homeostatic synaptic downscaling through coordinated transcriptional/epigenetic mechanism and Rab5c-mediated trafficking.