Presynaptic CaV2.1 calcium-dependent facilitation enables reliable auditory information transfer.

Activity-dependent modulation of presynaptic voltage-gated Ca2+ channels (CaV2) regulates Ca2+ influx to control neurotransmitter release and neuronal circuit output. Although CaV2.1 can undergo robust Ca2+-dependent facilitation (CDF), its contribution to information processing in central neuronal circuits remains unclear. Accurate auditory information processing requires precise and reliable synaptic transmission at high activity rates in the auditory brainstem. To determine if CaV2.1 CDF is a key regulator of high-fidelity synaptic transmission, we expressed CaV2.1 splice variants that are either CDF-capable (CaV2.1 37a) or CDF-incapable (CaV2.1 37b) at the calyx of Held presynaptic terminal. We found no difference in basal CaV2.1 currents or synaptic transmission. However, CaV2.1 37b terminals lacked CDF, synaptic facilitation and had a decreased reliability and precision of postsynaptic action-potential firing. Additionally, loss of CDF decreased the auditory brainstem response wave III amplitude. We propose that CaV2.1 CDF is essential for faithful auditory information transfer.