title: Hair cells use active zones with different voltage dependence of Ca2+ influx to decompose sounds into complementary neural codes.
abstract: For sounds of a given frequency, spiral ganglion neurons (SGNs) with different thresholds and dynamic ranges collectively encode the wide range of audible sound pressures. Heterogeneity of synapses between inner hair cells (IHCs) and SGNs is an attractive candidate mechanism for generating complementary neural codes covering the entire dynamic range. Here, we quantified active zone (AZ) properties as a function of AZ position within mouse IHCs by combining patch clamp and imaging of presynaptic Ca(2+) influx and by immunohistochemistry. We report substantial AZ heterogeneity whereby the voltage of half-maximal activation of Ca(2+) influx ranged over ∼20 mV. Ca(2+) influx at AZs facing away from the ganglion activated at weaker depolarizations. Estimates of AZ size and Ca(2+) channel number were correlated and larger when AZs faced the ganglion. Disruption of the deafness gene GIPC3 in mice shifted the activation of presynaptic Ca(2+) influx to more hyperpolarized potentials and increased the spontaneous SGN discharge. Moreover, Gipc3 disruption enhanced Ca(2+) influx and exocytosis in IHCs, reversed the spatial gradient of maximal Ca(2+) influx in IHCs, and increased the maximal firing rate of SGNs at sound onset. We propose that IHCs diversify Ca(2+) channel properties among AZs and thereby contribute to decomposing auditory information into complementary representations in SGNs.
authors.affiliation: Institute for Auditory Neuroscience & InnerEarLab, University Medical Center Göttingen, 37099 Goettingen, Germany; Göttingen Graduate School for Neurosciences and Molecular Biosciences, University of Göttingen, 37073 Goettingen, Germany; Bernstein Focus for Neurotechnology, University of Göttingen, 37073 Goettingen, Germany; Collaborative Research Center 889, University of Göttingen, 37099 Goettingen, Germany;
authors.forename: Tzu-Lun
authors.initials: TL
authors.lastname: Ohn
authors.affiliation: Institute for Auditory Neuroscience & InnerEarLab, University Medical Center Göttingen, 37099 Goettingen, Germany; Department of Otolaryngology, Washington University School of Medicine, St. Louis, MO 63110;
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rutherford
authors.affiliation: Göttingen Graduate School for Neurosciences and Molecular Biosciences, University of Göttingen, 37073 Goettingen, Germany; Collaborative Research Center 889, University of Göttingen, 37099 Goettingen, Germany; Auditory Systems Physiology Group, InnerEarLab, Department of Otolaryngology, University Medical Center Göttingen, 37099 Goettingen, Germany;
authors.forename: Zhizi
authors.initials: Z
authors.lastname: Jing
authors.affiliation: Institute for Auditory Neuroscience & InnerEarLab, University Medical Center Göttingen, 37099 Goettingen, Germany; Synaptic Nanophysiology Group, Max Planck Institute for Biophysical Chemistry, 37077 Goettingen, Germany; Center for Nanoscale Microscopy and Molecular Physiology of the Brain, University of Göttingen, 37073 Goettingen, Germany;
authors.forename: Sangyong
authors.initials: S
authors.lastname: Jung
authors.affiliation: Institute for Auditory Neuroscience & InnerEarLab, University Medical Center Göttingen, 37099 Goettingen, Germany; Göttingen Graduate School for Neurosciences and Molecular Biosciences, University of Göttingen, 37073 Goettingen, Germany;
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Duque-Afonso
authors.affiliation: Institute for Auditory Neuroscience & InnerEarLab, University Medical Center Göttingen, 37099 Goettingen, Germany;
authors.forename: Gerhard
authors.initials: G
authors.lastname: Hoch
authors.affiliation: Institute for Auditory Neuroscience & InnerEarLab, University Medical Center Göttingen, 37099 Goettingen, Germany; Göttingen Graduate School for Neurosciences and Molecular Biosciences, University of Göttingen, 37073 Goettingen, Germany;
authors.forename: Maria Magdalena
authors.initials: MM
authors.lastname: Picher
authors.affiliation: Institute of Pharmacy, Department of Pharmacology and Toxicology, University of Innsbruck, A-6020 Innsbruck, Austria; Center for Chemistry and Biomedicine, University of Innsbruck, A-6020 Innsbruck, Austria;
authors.forename: Anja
authors.initials: A
authors.lastname: Scharinger
authors.affiliation: Göttingen Graduate School for Neurosciences and Molecular Biosciences, University of Göttingen, 37073 Goettingen, Germany; Collaborative Research Center 889, University of Göttingen, 37099 Goettingen, Germany; Auditory Systems Physiology Group, InnerEarLab, Department of Otolaryngology, University Medical Center Göttingen, 37099 Goettingen, Germany;
authors.forename: Nicola
authors.initials: N
authors.lastname: Strenzke
authors.affiliation: Institute for Auditory Neuroscience & InnerEarLab, University Medical Center Göttingen, 37099 Goettingen, Germany; Göttingen Graduate School for Neurosciences and Molecular Biosciences, University of Göttingen, 37073 Goettingen, Germany; Bernstein Focus for Neurotechnology, University of Göttingen, 37073 Goettingen, Germany; Collaborative Research Center 889, University of Göttingen, 37099 Goettingen, Germany; Synaptic Nanophysiology Group, Max Planck Institute for Biophysical Chemistry, 37077 Goettingen, Germany; Center for Nanoscale Microscopy and Molecular Physiology of the Brain, University of Göttingen, 37073 Goettingen, Germany; Bernstein Center for Computational Neuroscience, University of Göttingen, 37073 Goettingen, Germany tmoser@gwdg.de.
authors.forename: Tobias
authors.initials: T
authors.lastname: Moser
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology; D005260:Female; D006199:Hair Cells, Auditory, Inner / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013016:Sound; D013136:Spiral Ganglion / Q000502:physiology; D013569:Synapses / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015220:Calcium Channels; C452599:Gipc3 protein, mouse; D002118:Calcium
keywords: auditory system; dynamic range; presynaptic heterogeneity; spiral ganglion neuron; synaptic strength