25dga010 10.3205/25dga010 urn:nbn:de:0183-25dga0101 Meeting Abstract Karagulyan Karagulyan Nare N

University Medical Center Göttingen, Institute for Auditory Neuroscience, Göttingen, Deutschland

author German Medical Science GMS Publishing House

Düsseldorf

610 20250318 engl This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). M0607 010 Deutsche Gesellschaft für Audiologie e. V. und ADANO 27. Jahrestagung der Deutschen Gesellschaft für Audiologie und Arbeitstagung der Arbeitsgemeinschaft Deutschsprachiger Audiologen, Neurootologen und Otologen Strukturierte Sitzung 4: Mechanismen der Schallempfindungsschwerhörigkeit Göttingen 20250319 20250321 010 TextMammalian auditory system responds to sound pressures ranging over 6 orders of magnitude. In the cochlea, primary auditory nerve fibers — spiral ganglion neurons (SGNs) — receive input from sensory inner hair cells (IHCs). Each IHC forms synapses with up to 20 SGNs . SGNs responding to the same sound frequency and potentially contacting one IHC display a large physiological diversity, whereby they differ in their spontaneous rates (SRs) of firing, sound thresholds, dynamic ranges and collectively code for the whole dynamic range of sound pressures: high-SR, low-threshold SGNs (innervating the pillar side of the IHC) respond to low sound pressures, while low-SR, high-threshold SGNs (innervating the modiolar side) are recruited at higher sound pressures. Position-dependent heterogeneity of IHC active zones (AZs) is a candidate mechanism for SGN diversity : pillar AZs, which are the input for the high SR fibers display small synaptic ribbons and low Ca2+ influx compared to the modiolar AZs . Yet the presynaptic Cav1.3 channels and the subsequent glutamate release at pillar AZs activate at low voltages, which is expected to drive high SRs and low thresholds in SGNs , , . The mechanisms establishing the gradients of AZ properties along the pillar-modiolar axis of the IHC remain largely unknown. Single synaptic Ca2+ and glutamate imaging at IHC AZs combined with patch-clamp, as well as position dependent immunofluorescence analysis of AZ proteins allow for the thorough analysis of presynaptic heterogeneity in IHCs of genetically modified mice , . We recently demonstrated that the loss of glutamatergic signaling and exocytosis in Vglut3-deficient and otoferlin-mutant mice does not disrupt IHC presynaptic heterogeneity . Additionally, assessment of auditory function in-vivo by recording auditory brainstem responses (ABRs) and single SGN firing allows us to relate SGN diversity and presynaptic heterogeneity. For example, we have observed increased spontaneous firing rates and mildly reduced ABR thresholds in mice displaying hyperpolarized activation of presynaptic Ca2+ channels due to a point mutation in Cav1.3 channels, highlighting the regulation of SGN spontaneous and evoked firing by presynaptic Cav1.3 gating and indicating that the heterogeneous voltage dependence of Ca2+ channel activation at IHCs AZs contributes to the firing diversity of SGNs (Karagulyan et al., unpublished). Jaime Tobón LM Moser T Bridging the gap between presynaptic hair cell function and neural sound encoding 2024 Elife RP93749 Jaime Tobón LM, Moser T. Bridging the gap between presynaptic hair cell function and neural sound encoding. Elife. 2024 Dec 24;12:RP93749. DOI: 10.7554/eLife.93749 http://dx.doi.org/10.7554/eLife.93749 Karagulyan N Moser T Synaptic activity is not required for establishing heterogeneity of inner hair cell ribbon synapses 2023 Front Mol Neurosci 1248941 Karagulyan N, Moser T. Synaptic activity is not required for establishing heterogeneity of inner hair cell ribbon synapses. Front Mol Neurosci. 2023 Sep 6;16:1248941. DOI: 10.3389/fnmol.2023.1248941 http://dx.doi.org/10.3389/fnmol.2023.1248941 Meyer AC Frank T Khimich D Hoch G Riedel D Chapochnikov NM Yarin YM Harke B Hell SW Egner A Moser T Tuning of synapse number, structure and function in the cochlea 2009 Nat Neurosci 444-53 Meyer AC, Frank T, Khimich D, Hoch G, Riedel D, Chapochnikov NM, Yarin YM, Harke B, Hell SW, Egner A, Moser T. Tuning of synapse number, structure and function in the cochlea. Nat Neurosci. 2009 Apr;12(4):444-53. DOI: 10.1038/nn.2293 http://dx.doi.org/10.1038/nn.2293 Moser T Karagulyan N Neef J Jaime Tobón LM Diversity matters - extending sound intensity coding by inner hair cells via heterogeneous synapses 2023 EMBO J e114587 Moser T, Karagulyan N, Neef J, Jaime Tobón LM. Diversity matters - extending sound intensity coding by inner hair cells via heterogeneous synapses. EMBO J. 2023 Dec 1;42(23):e114587. DOI: 10.15252/embj.2023114587 http://dx.doi.org/10.15252/embj.2023114587 Ohn TL Rutherford MA Jing Z Jung S Duque-Afonso CJ Hoch G Picher MM Scharinger A Strenzke N Moser T Hair cells use active zones with different voltage dependence of Ca2+ influx to decompose sounds into complementary neural codes 2016 Proc Natl Acad Sci U S A E4716-25 Ohn TL, Rutherford MA, Jing Z, Jung S, Duque-Afonso CJ, Hoch G, Picher MM, Scharinger A, Strenzke N, Moser T. Hair cells use active zones with different voltage dependence of Ca2+ influx to decompose sounds into complementary neural codes. Proc Natl Acad Sci U S A. 2016 Aug 9;113(32):E4716-25. DOI: 10.1073/pnas.1605737113 http://dx.doi.org/10.1073/pnas.1605737113 Özçete ÖD Moser T A sensory cell diversifies its output by varying Ca2+ influx-release coupling among active zones 2021 EMBO J e106010 Özçete ÖD, Moser T. A sensory cell diversifies its output by varying Ca2+ influx-release coupling among active zones. EMBO J. 2021 Mar 1;40(5):e106010. DOI: 10.15252/embj.2020106010 http://dx.doi.org/10.15252/embj.2020106010 0 0 0 0