Chen et al. investigate the coupling between presynaptic Ca²⁺ channels and release sensors at inhibitory GABAergic synapses in the cerebellum, specifically at the basket cell (BC)-Purkinje cell (PC) synapse. They find that during development, the coupling distance decreases, but the reliance on P/Q-type Ca²⁺ channels remains constant. Structural analysis using freeze-fracture replica labeling (FRL) and transmission electron microscopy (EM) reveals that presynaptic P/Q-type Ca²⁺ channels form nanoclusters throughout development, while docked vesicles cluster only at later stages. Modeling suggests a transformation from random to clustered coupling nanotopography, indicating that presynaptic signaling approaches a point-to-point configuration, optimizing speed, reliability, and energy efficiency of synaptic transmission. The study highlights the importance of coupling nanotopography in inhibitory synapses and provides insights into the molecular mechanisms underlying these developmental changes.Chen et al. investigate the coupling between presynaptic Ca²⁺ channels and release sensors at inhibitory GABAergic synapses in the cerebellum, specifically at the basket cell (BC)-Purkinje cell (PC) synapse. They find that during development, the coupling distance decreases, but the reliance on P/Q-type Ca²⁺ channels remains constant. Structural analysis using freeze-fracture replica labeling (FRL) and transmission electron microscopy (EM) reveals that presynaptic P/Q-type Ca²⁺ channels form nanoclusters throughout development, while docked vesicles cluster only at later stages. Modeling suggests a transformation from random to clustered coupling nanotopography, indicating that presynaptic signaling approaches a point-to-point configuration, optimizing speed, reliability, and energy efficiency of synaptic transmission. The study highlights the importance of coupling nanotopography in inhibitory synapses and provides insights into the molecular mechanisms underlying these developmental changes.