The study investigates the developmental transformation of Ca²⁺ channel-vesicle nanotopography at a central GABAergic synapse. It reveals that during development, the coupling between presynaptic Ca²⁺ channels and release sensors changes from a more random organization to a more precise point-to-point configuration. Despite a constant reliance on P/Q-type Ca²⁺ channels, the sensitivity to Ca²⁺ chelators decreases during development. Structural analysis shows that Ca²⁺ channel clusters persist throughout development, while docked vesicles become clustered at later stages. Modeling suggests a shift from a random to a clustered coupling nanotopography, indicating that presynaptic signaling becomes more efficient and reliable during development. The study combines paired recordings, structural analysis, and modeling to show that synaptic efficacy and kinetics change during development, with presynaptic action potentials shortening and release probability decreasing. The number of functional release sites increases, and the quantal size decreases, but the quantal content remains relatively stable. The study also shows that the coupling between Ca²⁺ channels and release sensors tightens during development, with a reduction in the sensitivity of exogenous Ca²⁺ chelators. Structural analysis reveals that the number of active zones and docked vesicles increases during development, and the distribution of docked vesicles becomes more clustered. The study concludes that the coupling nanotopography transforms from a more random to a more clustered configuration during development, optimizing the speed, reliability, and energy efficiency of synaptic transmission.The study investigates the developmental transformation of Ca²⁺ channel-vesicle nanotopography at a central GABAergic synapse. It reveals that during development, the coupling between presynaptic Ca²⁺ channels and release sensors changes from a more random organization to a more precise point-to-point configuration. Despite a constant reliance on P/Q-type Ca²⁺ channels, the sensitivity to Ca²⁺ chelators decreases during development. Structural analysis shows that Ca²⁺ channel clusters persist throughout development, while docked vesicles become clustered at later stages. Modeling suggests a shift from a random to a clustered coupling nanotopography, indicating that presynaptic signaling becomes more efficient and reliable during development. The study combines paired recordings, structural analysis, and modeling to show that synaptic efficacy and kinetics change during development, with presynaptic action potentials shortening and release probability decreasing. The number of functional release sites increases, and the quantal size decreases, but the quantal content remains relatively stable. The study also shows that the coupling between Ca²⁺ channels and release sensors tightens during development, with a reduction in the sensitivity of exogenous Ca²⁺ chelators. Structural analysis reveals that the number of active zones and docked vesicles increases during development, and the distribution of docked vesicles becomes more clustered. The study concludes that the coupling nanotopography transforms from a more random to a more clustered configuration during development, optimizing the speed, reliability, and energy efficiency of synaptic transmission.