RIM-BP2 regulates Ca²⁺ channel abundance and neurotransmitter release at hippocampal mossy fiber terminals.

ABSTRACT: 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. In order to dissect the role of RIM-BP2 at mammalian cortical synapses having low release probability, we applied direct electrophysiological recording and super-resolution imaging to hippocampal mossy fiber terminals of RIM-BP2 knockout (KO) mice. By using direct presynaptic recording, we found the reduced Ca²⁺ currents. The measurements of excitatory postsynaptic currents (EPSCs) and presynaptic capacitance suggested that the initial release probability was lowered because of the reduced Ca²⁺ influx and impaired fusion competence in RIM-BP2 KO. Nevertheless, larger Ca²⁺ influx restored release partially. Consistent with presynaptic recording, STED microscopy suggested less abundance of P/Q-type Ca²⁺ channels at AZs deficient in RIM-BP2. Our results suggest that the RIM-BP2 regulates both Ca²⁺ channel abundance and transmitter release at mossy fiber synapses.

SUBMITTER: Miyano R 

PROVIDER: S-EPMC10945523 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature