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Presynaptic Ca V 2.1 calcium dependent facilitation is essential for faithful auditory information transfer
Preprint   Open access

Presynaptic Ca V 2.1 calcium dependent facilitation is essential for faithful auditory information transfer

Mohammed Al-Yaari, Jianing Li, Christian Keine, Bryce Hunger, Marlan R. Hansen and Samuel M. Young
bioRxiv
Cold Spring Harbor Laboratory Preprints
04/24/2026
DOI: 10.64898/2026.04.24.720705
url
https://doi.org/10.64898/2026.04.24.720705View
Preprint (Author's original) This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

Activity-dependent modulation of presynaptic voltage-gated Ca 2+ channels (Ca V 2) regulates Ca 2+ influx to control neuronal circuit output. Although Ca V 2.1 can undergo robust Ca 2+ dependent facilitation (CDF), whether it occurs in native central nervous system neuronal circuits is disputed. Accurate auditory information processing requires precise and reliable synaptic transmission at high activity rates in the auditory brainstem. To determine if Ca V 2.1 CDF is a key regulator of high-fidelity synaptic transmission, we expressed Ca V 2.1 splice variants capable (Ca V 2.1 37a) or incapable (Ca V 2.1 37b) of CDF at the calyx of Held presynaptic terminal in the auditory brainstem. We found no difference in basal Ca V 2.1 currents or synaptic transmission. However, Ca V 2.1 37b terminals lacked CDF, synaptic facilitation and had a decreased reliability and precision of postsynaptic action-potential firing. Additionally, the Wave III amplitude of the auditory brainstem responses was reduced. We propose that Ca V 2.1 CDF is essential for accurate auditory information processing.

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