| dc.contributor.advisor | Moser, Tobias Prof. Dr. | |
| dc.contributor.author | Jaime Tobon, Lina Maria | |
| dc.date.accessioned | 2021-10-26T12:53:50Z | |
| dc.date.available | 2021-11-02T00:50:04Z | |
| dc.date.issued | 2021-10-26 | |
| dc.identifier.uri | http://hdl.handle.net/21.11130/00-1735-0000-0008-595A-0 | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-8905 | |
| dc.language.iso | eng | de |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
| dc.subject.ddc | 570 | de |
| dc.title | Molecular physiology of sound encoding | de |
| dc.type | cumulativeThesis | de |
| dc.contributor.referee | Neher, Erwin Prof. Dr. | |
| dc.date.examination | 2019-10-24 | |
| dc.description.abstracteng | Inner hair cells (IHC) are responsible for transforming mechanical sound-borne vibrations into electrical signals and conveying this information to the afferent spiral ganglion neurons (SGNs). Upon stimulation, the receptor potential triggers the opening of voltage-gated Ca2+ channels, mediating the fusion of vesicles and the consequent release of neurotransmitter from the presynaptic active zone to the postsynaptic bouton. In vivo recordings from SGNs revealed highly synchronized onset responses and indefatigably sustained firing rates. A plethora of techniques has been used to understand how IHCs accomplish this impressive performance of neurotransmitter release, and which mechanisms establish the diversity of auditory nerve fibers (ANFs) responses to stimulation. This thesis provides further insight into the molecular physiology of sound encoding.
First, synaptic transmission at individual murine IHC afferent synapses was studied using paired IHC-bouton patch clamp recordings in near physiological conditions. Synapses contacting the pillar side of the IHC had higher rates of spontaneous EPSCs that were characterized by larger amplitudes yet similar charges. High spontaneous rates (SR) synapses had significantly lower voltage thresholds of release and tended to have shorter synaptic delays, as well as faster recovery from readily releasable pool (RRP) depletion. Furthermore, this study corroborated that a Ca2+-nanodomain-like control of exocytosis operates at IHCs synapses.
Second, collaborators and I studied synaptic transmission in IHC synapses from RIBEYE knockout (KO) mice. Their ribbonless synapses were characterized by several small active zones opposing each postsynaptic density. In vivo ANFs recordings revealed an impaired synaptic transmission, characterized by lower spontaneous and evoked firing rates, lower temporal precision and a slower recovery from adaptation. Ca2+ imaging of individual active zones showed that the Ca2+ channels required more depolarized potentials to activate. Consequently, weak depolarizations during perforated patch-clamp recordings resulted in reduced exocytosis compared to wildtype (Wt). We postulated a role of the ribbon in synaptic vesicle replenishment and Ca2+ channel regulation.
Third, collaborators and I studied the role of endophilin-A1-3, endocytic adaptor proteins, in IHCs. Perforated patch-clamp recordings from organotypic cultures and from explanted organs of Corti revealed lower Ca2+ influx, impaired sustained exocytosis and slower endocytic membrane retrieval in Endophilin-A-deficient IHCs. At the ultrastructural level, the IHC active zones had lower counts of synaptic vesicles, but increased numbers of coated structures and endosome-like vacuoles. In addition, we postulated a molecular interaction between endophilin-A1 and otoferlin based on co-immunoprecipitation. We proposed a positive role of endophilin-A in the modulation of Ca2+ channels, and in synaptic vesicle recycling, likely via coupling of exo- and endocytosis, membrane retrieval, synaptic vesicle uncoating and reformation. | de |
| dc.contributor.coReferee | Lindau, Manfred Prof. Dr. | |
| dc.contributor.thirdReferee | Schmidt, Manuela Dr. | |
| dc.contributor.thirdReferee | Dresbach, Thomas Prof. Dr. | |
| dc.contributor.thirdReferee | Göpfert, Martin Prof. Dr. | |
| dc.subject.eng | Inner hair cells | de |
| dc.subject.eng | Synaptic transmission | de |
| dc.subject.eng | Postsynaptic bouton | de |
| dc.subject.eng | Auditory neuroscience | de |
| dc.subject.eng | Paired patch-clamp recordings | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-21.11130/00-1735-0000-0008-595A-0-4 | |
| dc.affiliation.institute | Göttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB) | de |
| dc.subject.gokfull | Biologie (PPN619462639) | de |
| dc.description.embargoed | 2021-11-02 | |
| dc.identifier.ppn | 1775525384 | |