Journal article
Presynaptic Ca V 2.1 calcium-dependent facilitation enables reliable auditory information transfer
Cell reports (Cambridge), Vol.45(9), 117874
08/22/2026
DOI: 10.1016/j.celrep.2026.117874
PMID: 42632018
Abstract
Summary
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.
Details
- Title: Subtitle
- Presynaptic Ca V 2.1 calcium-dependent facilitation enables reliable auditory information transfer
- Creators
- Mohammed Al-Yaari - University of IowaJianing Li - University of North Carolina at Chapel HillChristian Keine - University of IowaBryce Hunger - University of IowaMarlan R Hansen - University of IowaSamuel M Young Jr
- Resource Type
- Journal article
- Publication Details
- Cell reports (Cambridge), Vol.45(9), 117874
- DOI
- 10.1016/j.celrep.2026.117874
- PMID
- 42632018
- NLM abbreviation
- Cell Rep
- ISSN
- 2639-1856
- eISSN
- 2211-1247
- Publisher
- Elsevier
- Grant note
- National Institute on Deafness and Other Communication Disorders: R01 DC014093, R01 DC018488, R01 DC012578 National Institute of Neurological Disorders and Stroke: R01 NS110742 National Center for Advancing Translational Sciences: UM1TR004403 University of North Carolina at Chapel Hill Deutsche Forschungsgemeinschaft (DFG): 420075000
This work was supported by the National Institute on Deafness and Other Communication Disorders (R01 DC014093 to S.M.Y., Jr., R01 DC018488 to M.R.H., and R01 DC012578 to M.R.H.) , the National Institute of Neurological Disorders and Stroke (R01 NS110742 to S.M.Y., Jr.) , the National Center for Advancing Translational Sciences (UM1TR004403 to M.R.H.) , start-up funds from the University of North Carolina at Chapel Hill (S.M.Y., Jr.) and the Deutsche Forschungsgemeinschaft (DFG, 420075000, to C.K.) . We thank members of the Young Lab for their comments on the manuscript. We thank Hao Li and Dr. Joe Zhou for help with HdAd production and titering. We thank Dr. Phillip Ng for HdAd packaging plasmids. Part of this study was initiated and performed at the University of Iowa.
- Language
- English
- Date published
- 08/22/2026
- Academic Unit
- Molecular Physiology and Biophysics; Neurosurgery; Otolaryngology
- Record Identifier
- 9985220843702771
Metrics
3 Record Views