RIM-BP2 is required for rapid neurotransmitter release through regulation of Ca2+ channel clustering at hippocampal mossy fiber terminals

Synaptic vesicles dock and fuse at the presynaptic active zone (AZ), the specialized site for transmitter release. AZ proteins play multiple roles such as recruitment of Ca2+ channels as well as synaptic vesicle docking, priming and fusion. However, the precise role of each AZ protein type remains unknown. At phasic synapses having high release probability, Rab3-interacting molecule-binding protein2 (RIM-BP2) is known to affect Ca2+ channel localization at AZs. In order to dissect the role of RIM-BP2 at tonic synapses having low release probability, we applied electrophysiological recording and super-resolution imaging to hippocampal mossy fiber terminals of RIM-BP2 KO mice. By using whole cell capacitance measurements, we found that reduced Ca2+ currents were responsible for the decreased rates of transmitter release in RIM-BP2 KO terminals. Consistently, STED microscopy pictured lower densities of P/Q-type Ca2+ channels at AZs deficient in RIM-BP2. Our results suggest that the RIM-BP2 function differs between phasic and tonic synapses. ### Competing Interest Statement The authors have declared no competing interest.