Short-term facilitation at a detonator synapse requires the distinct contribution of multiple types of voltage-gated calcium channels

Abstract

Neuronal calcium elevations are shaped by several key parameters, including the properties, density, and the spatial location of voltagegated calcium channels (VGCCs). These features allow presynaptic terminals to translate complex firing frequencies and tune the amount of neurotransmitter released. Although synchronous neurotransmitter release relies on both P/Q-and N-type VGCCs at hippocampal mossy fiber-CA3 synapses, the specific contribution of VGCCs to calcium dynamics, neurotransmitter release, and short-term facilitation remains unknown. Here, we used random-access two-photon calcium imaging together with electrophysiology in acute mouse hippocampal slices to dissect the roles of P/Q-and N-type VGCCs. Our results show that N-type VGCCs control glutamate release at a limited number of release sites through highly localized Ca2+ elevations and support short-term facilitation by enhancing multivesicular release. In contrast, Ca2+ entry via P/Q-type VGCCs promotes the recruitment of additional release sites through spatially homogeneous Ca2+ elevations. Altogether, our results highlight the specialized contribution of P/Q-and N-types VGCCs to neurotransmitter release.