Title | Short-Term Facilitation at a Detonator Synapse Requires the Distinct Contribution of Multiple Types of Voltage-Gated Calcium Channels. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Chamberland, Simon, Alesya Evstratova, and Katalin Toth |
Journal | J Neurosci |
Volume | 37 |
Issue | 19 |
Pagination | 4913-4927 |
Date Published | 2017 May 10 |
ISSN | 1529-2401 |
Keywords | Animals, Calcium, Calcium Signaling, Cells, Cultured, Excitatory Postsynaptic Potentials, Female, Ion Channel Gating, Long-Term Potentiation, Male, Mice, Mice, Inbred C57BL, Neurons, Potassium Channels, Voltage-Gated, Presynaptic Terminals |
Abstract | Neuronal calcium elevations are shaped by several key parameters, including the properties, density, and the spatial location of voltage-gated 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 Caelevations and support short-term facilitation by enhancing multivesicular release. In contrast, Caentry via P/Q-type VGCCs promotes the recruitment of additional release sites through spatially homogeneous Caelevations. Altogether, our results highlight the specialized contribution of P/Q- and N-types VGCCs to neurotransmitter release.In presynaptic terminals, neurotransmitter release is dynamically regulated by the transient opening of different types of voltage-gated calcium channels. Hippocampal giant mossy fiber terminals display extensive short-term facilitation during repetitive activity, with a large several fold postsynaptic response increase. Though, how giant mossy fiber terminals leverage distinct types of voltage-gated calcium channels to mediate short-term facilitation remains unexplored. Here, we find that P/Q- and N-type VGCCs generate different spatial patterns of calcium elevations in giant mossy fiber terminals and support short-term facilitation through specific participation in two mechanisms. Whereas N-type VGCCs contribute only to the synchronization of multivesicular release, P/Q-type VGCCs act through microdomain signaling to recruit additional release sites. |
DOI | 10.1523/JNEUROSCI.0159-17.2017 |
Alternate Journal | J. Neurosci. |
PubMed ID | 28411270 |