Input-specific deployment of the active zone scaffold RIM tunes synaptic release probability and plasticity

The multidomain scaffold RIM (Rab3-interacting molecule) is widely viewed as a broadly required organizer of the presynaptic active zone, clustering voltage-gated Ca 2+ (Ca v 2) channels, priming synaptic vesicles, and supporting neurotransmitter release. Whether this reliance is uniform across synapses with distinct release probabilities, however, has been difficult to resolve at convergent inputs. Here, using neurotoxin-based silencing to isolate transmission at the Drosophila neuromuscular junction, we show that the requirement for RIM is highly input-specific: RIM is essential to empower transmission at a high–release probability phasic synapse, yet is largely dispensable at a neighboring low–release probability tonic synapse. This specificity extends to plasticity: RIM is required for acute homeostatic potentiation at the phasic input, but not for chronic potentiation at the tonic input. Super-resolution imaging reveals that RIM is positioned closer to Ca v 2 channels at phasic synapses and, during acute plasticity, coordinates their nanoscale reorganization to drive the rapid expansion of the readily releasable pool.