| dc.contributor.advisor | Strenzke, Nicola Dr. | |
| dc.contributor.author | Yamanbaeva, Gulnara | |
| dc.date.accessioned | 2018-08-10T09:38:59Z | |
| dc.date.available | 2018-08-10T09:38:59Z | |
| dc.date.issued | 2018-08-10 | |
| dc.identifier.uri | http://hdl.handle.net/11858/00-1735-0000-002E-E479-4 | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-7005 | |
| dc.language.iso | eng | de |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
| dc.subject.ddc | 570 | de |
| dc.title | Sound encoding in mutant mice with disrupted action potential generation | de |
| dc.type | doctoralThesis | de |
| dc.contributor.referee | Strenzke, Nicola Dr. | |
| dc.date.examination | 2017-08-21 | |
| dc.description.abstracteng | Auditory tasks like sound localization or speech recognition require reliable and temporally precise neuronal sound encoding. The neuronal code must accurately preserve signal properties such as intensity and timing. Electrophysiological recordings from single spiral ganglion neuron provide a detailed picture of how auditory sensory information is encoded. Analysis of the response pattern of the cochlear nucleus cells after receiving sensory information encoded at peripheral synapses gives insight into the auditory systems primary processing. Investigation of the response patterns of spiral ganglion neurons and cochlear nucleus cells after mutations in pre- and post-synaptic proteins of inner hair cell ribbon synapse helps to reveal a role of these proteins in synaptic transmission and sound encoding. The synaptic sound encoding and underlying primary mechanisms at the synapses in the central and peripheral auditory system were studied through a combination of in vivo electrophysiology, confocal and high-resolution STED microscopy, and psychophysiological behavioral experiments for the detection of silent gaps in noise and thresholds sensitivity. This thesis investigates the role of four proteins (WRB, otoferlin, ßIV-spectrin, PSD-95) that are crucial for the action potential generation and neuronal sound encoding. WRB was found to regulate the otoferlin expression and localization and hence plays an essential role for inner hair cell exocytosis. Otoferlin was indicated to play a key role in synaptic vesicles replenishment. Its mutation was found to lead to the gap detection impairment in OtofI515T/I515T mice. The gap detection impairment was attributed to the stronger adaptation of acoustically evoked spiral ganglion neuron spike rates, as well as delayed recovery of the sound onset response in spiral ganglion neurons. A similar mechanism might underlie the speech comprehension difficulties in human patients carrying the same mutation. ßIV-spectrin was found to be crucial for the action potential generation in spiral ganglion neuron. PSD-95 in spiral ganglion neuron was indicated to be essential for proper AMPA receptors clustering and their recycling at the post-synaptic membrane and hence plays a role in spikes generation and synaptic sound encoding. | de |
| dc.contributor.coReferee | Löwel, Siegrid Prof. Dr. | |
| dc.subject.eng | WRB | de |
| dc.subject.eng | PSD-95 | de |
| dc.subject.eng | AMPA receptors recycling | de |
| dc.subject.eng | ßIV-spectrin | de |
| dc.subject.eng | single unit in vivo recording | de |
| dc.subject.eng | spiral ganglion neuron | de |
| dc.subject.eng | in vivo electrophysiology | de |
| dc.subject.eng | STED microscopy | de |
| dc.subject.eng | inner hair cell ribbon synapse | de |
| dc.subject.eng | otoferlin | de |
| dc.subject.eng | cochlear nucleus neuron | de |
| dc.subject.eng | action potential generation | de |
| dc.subject.eng | sound encoding | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-11858/00-1735-0000-002E-E479-4-2 | |
| dc.affiliation.institute | Göttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB) | de |
| dc.subject.gokfull | Biologie (PPN619462639) | de |
| dc.identifier.ppn | 1030406111 | |