The emergence of comprehensive connectomes in organisms, like Caenorhabditis elegans, Drosophila, and the mouse, is transforming our understanding of neural circuit architecture. Manipulating these circuits noninvasively, however, remains a major challenge. Optogenetics is a promising neuromodulation technique but requires external light to activate neurons within the target tissue. To address this, we recently developed and deployed photon-assisted synaptic transmission, or short PhAST, a system of bioluminescence-driven optogenetics, where light is generated directly within presynaptic neuronal compartments through luciferase-luciferin reactions and activates postsynaptically expressed channelrhodopsins. Using the PhAST strategy in C. elegans, we demonstrated activity-dependent, transsynaptic activation of channelrhodopsins to restore disrupted signaling without external light. Photon emission from luciferases, broadly distributed along axons and gated by intracellular messengers such as calcium, enables flexible, synapse-independent information transfer, even under conditions of vesicular transmission failure. This modular system not only bypasses the physical limitations of traditional optogenetics but also sets the stage for programmable, stimulus-responsive networks that leverage intrinsic signaling dynamics for precision neuromodulation.