//     VOGL GROUP

 

 

 

Keywords: auditory system, cochlea, hair cells, ribbon synapses, synaptic transmission, synaptogenesis, developmental plasticity, hearing loss

//     AIM

Ribbon synapses of auditory inner hair cells (IHCs) transmit acoustic information with exquisite temporal precision. Here, synaptic sound encoding – i.e., the translation of physical sound waves into neural code – is achieved by ultrafast and tightly regulated presynaptic exocytosis of glutamate-filled synaptic vesicles onto postsynaptic spiral ganglion neurons (SGNs). In this system, presynaptic ribbons play a major role in orchestrating synaptic release (e.g., by clustering presynaptic L-type Ca_V1.3 Ca²⁺ channels and other components of the release machinery) and rapid vesicular replenishment to ensure a constant supply of vesicles and hence prevents synaptic fatigue.

Within the past decade, a range of molecular scaffolds and key regulators of these presynaptic complexes could be identified and have deepened our understanding of this unconventional synapse. However, fundamental aspects of auditory ribbon synapse developmental assembly – such as ribbon precursor trafficking and active zone structural plasticity – remain largely elusive.

Hence, our lab aims for a better understanding of these cell biological processes using a broad range of live-cell and fixed tissue analysis methods.

//     METHODS

• Advanced microscopy techniques (confocal, super-resolution STED, 2-photon microscopy)
• Live-cell imaging (single particle tracking, Ca²⁺ imaging)
• Neuronal fiber tracing
• Patch clamp electrophysiology
• Optogenetics
• Primary and secondary tissue culture (organotypic, cell lines)

 

//     RESEARCH TOPICS

• Developmental assembly of auditory ribbon synapses
• Modes of activity-dependent structural plasticity at auditory ribbon synapses
• Identification and characterization of novel deafness genes
• Cochlear anatomy and neuronal connectivity
• Regulation of presynaptic neurotransmitter release at auditory ribbon synapses

 

//     LAB MEMBERS

• Group leader: Christian Vogl
• Doctoral candidates:
  • • • Roos Anouk Voorn
      • Victoria Christine Halim
      • Jan Frederik Ahrend
• Technical support:
  • • • Theresa Martha

 

//     ADDRESS

Auditory Neuroscience Group
Division of Physiology
Department Physiology and Medical Physics
Medical University of Innsbruck
Schöpfstr. 41/1st floor, office 154
A-6020 Innsbruck

 

//     SELECTED PUBLICATIONS

1.) Vogl C^#, Neef J, Wichmann C^# (2022) Methods for multiscale structural and functional analysis of the mammalian cochlea. Mol Cell Neurosci. 2022 Mar 11;103720. doi: 10.1016/j.mcn.2022.103720. (Review)

2.) Rankovic V^#,*, Vogl C^#,*, Dörje NM, Bahader I, Duque-Afonso CJ, Thirumalai A, Weber T, Kusch K, Strenzke N, Moser T^* (2021): Overloaded adeno-associated virus as a novel gene therapeutic tool for otoferlin-related deafness. Front. Mol. Neurosci. Jan 7;13:600051. doi: 10.3389/fnmol.2020.600051. eCollection 2020.

3.) Voorn RA & Vogl C^# (2020) Molecular assembly and structural plasticity of sensory ribbon synapses – a presynaptic perspective. Int.J.Mol.Sci. 2020,21,8758; doi:10.3390/ijms21228758. (Review)

4.) Kleinlogel S*, Vogl C*, Jeschke M*, Neef J & Moser T (2020) Emerging approaches for restoration of hearing and vision. Physiol Rev 2020 Oct 1;100(4):1467-1525. doi: 10.1152/physrev.00035.2019. (Review)

5.) Michanski S, Smaluch K, Steyer AM, Chakrabarti R, Setz C, Oestreicher D, Fischer C, Möbius W, Moser T, Vogl C^#, Wichmann C^# (2019): Mapping developmental maturation of inner hair cell ribbon synapses in the apical mouse cochlea. Proc Natl Acad Sci U S A. 2019 Mar 26;116(13):6415-6424. doi: 10.1073/pnas

6.) Kroll J*, Jaime Tobón LM*, Vogl C*, Neef J, Kondratiuk I, König M, Strenzke N, Wichmann C, Milosevic I, Moser T (2019): Endophilin-A regulates presynaptic Ca²⁺ influx and synaptic vesicle recycling in auditory hair cells. EMBO J 2019 Mar 1;38(5). pii: e100116. doi: 10.15252/embj.2018100116.

7.) Vogl C^#, Butola T, Haag N, Hausrat TJ, Leitner MG, Moutschen M, Lefebvre PP, Speckmann C, Garrett L, Becker L, Fuchs H, Hrabe de Angelis M, Nietzsche S, Kessels MM, Oliver D, Kneussel M, Kilimann MW, Strenzke N^# (2017): The BEACH protein LRBA is Required for Hair Bundle Maintenance in Cochlear Hair Cells and for Hearing. EMBO Rep. 2017 Sep 11. pii: e201643689. doi: 10.15252/embr.201643689

8.) Vogl C*, Panou I*, Yamanbaeva G*, Wichmann C*, Mangosing S*, Vilardi F*, Indzhykulian AA*, Pangršič T*, Santarelli R, Rodriguez-Ballesteros M, Weber T, Jung S, Wu X, Wojcik SM, Kwan KY, del Castillo I, Schwappach B, Strenzke N, Corey DP, Lin SY, Moser T (2016): Tryptophan-rich basic protein (WRB) mediates insertion of the tail-anchored protein otoferlin and is required for hair cell exocytosis and hearing. EMBO J. 2016 Jul 25. pii: e201593565. doi 10.15252/embj.201593565

9.) Vogl C^#, Cooper B, Neef J, Strenzke N, Reisinger E, Reim K, Brose N, Rhee JS, Moser T*, Wichmann C^# (2015): Unconventional molecular regulation of synaptic vesicle replenishment in cochlear inner hair cells. J Cell Sci. 2015 Feb 15;128(4):638-44. doi: 10.1242/jcs.162099

10.) Vogl C, Mochida S, Wolff C, Whalley BJ, Stephens GJ (2012): The SV2A Ligand Levetiracetam Inhibits Presynaptic Ca²⁺ Channels Via an Intracellular Pathway. Mol Pharmacol. 2012 Aug;82(2):199-208.

*equal contribution; ^#shared correspondence

Full publication list

//     FUNDING SOURCES

• Deutsche Forschungsgemeinschaft (DFG; Projekt VO 2466/1-1)
• Fonds zur Förderung Wissenschaftlicher Forschung (FWF)
• Otto Creutzfeldt Fellowship (Elisabeth und Helmut Uhl Foundation)

 

// JOURNAL COVERS