Ultrafast Multichannel Optogenetic Stimulation of the Auditory Pathway for Optical Cochlear Implants

Keppeler, Daniel

dc.contributor.advisor	Moser, Tobias Prof. Dr.
dc.contributor.author	Keppeler, Daniel
dc.date.accessioned	2019-01-14T09:35:59Z
dc.date.available	2019-12-18T23:50:02Z
dc.date.issued	2019-01-14
dc.identifier.uri	http://hdl.handle.net/11858/00-1735-0000-002E-E55A-2
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-7231
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-7231
dc.language.iso	eng	de
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc	570	de
dc.title	Ultrafast Multichannel Optogenetic Stimulation of the Auditory Pathway for Optical Cochlear Implants	de
dc.type	doctoralThesis	de
dc.contributor.referee	Schlüter, Oliver Prof. Dr. Dr.
dc.date.examination	2018-12-17
dc.description.abstracteng	In case of profound sensorineural hearing loss and deafness, cochlear implants (CIs) partially restore hearing and provide missing auditory information to the brain. Electrical stimulation of the spiral ganglion neurons (SGNs) enables speech understanding in the majority of the approximately 500,000 CI users. However, the utility of current clinical CIs is limited by their wide current spread resulting in limited coding of spectral information. As light can be better confined in space, optical CIs (oCIs) promise lower spread of excitation in the cochlea which might enable better speech comprehension in noisy background as well as music appreciation. This thesis focuses on five key aspects for development of future CIs in research and clinical translation: (1) Characterizing a novel ultrafast optogenetic tool in the mouse cochlea: Chronos, a channelrhodopsin (ChR) supporting high temporal fidelity prerequisite for auditory coding. (2) Improving spiral ganglion neuron (SGN) expression levels and SGN targeting by the recently discovered adeno-associated virus (AAV)-PHP.B. (3) Enhancing ChR trafficking to the plasma membrane (Chronos—ES/TS). (4) Evaluating cochlear space for optical probes in common animal models employing phase-contrast X-ray tomography thereby providing a comprehensive library for morphological parameters relevant for CI development in rodents and non-human primates. (5) Establishing first multichannel oCIs based on microfabricated light-emitting diode (LED) arrays in channelrhodopsin-2 (ChR2)-expressing rats and their functional validation utilizing auditory brainstem responses (ABRs). Taken together, the thesis demonstrates feasibility of optogenetic cochlea stimulation by expressing the ultrafast ChR Chronos and LED-based multichannel oCIs.	de
dc.contributor.coReferee	Willig, Katrin Dr.
dc.contributor.thirdReferee	Dresbach, Thomas Prof. Dr.
dc.contributor.thirdReferee	Heinrich, Ralf Prof. Dr.
dc.contributor.thirdReferee	Dean, Camin Ph.D.
dc.subject.eng	optogenetic	de
dc.subject.eng	cochlea	de
dc.subject.eng	implant	de
dc.subject.eng	CI	de
dc.subject.eng	channelrhodopsin	de
dc.subject.eng	ChR2	de
dc.subject.eng	Chronos	de
dc.subject.eng	AAV	de
dc.subject.eng	adeno-associated virus	de
dc.subject.eng	CBCT	de
dc.subject.eng	microCT	de
dc.subject.eng	X-ray	de
dc.subject.eng	optical	de
dc.subject.eng	LED	de
dc.subject.eng	microLED	de
dc.subject.eng	auditory	de
dc.subject.eng	opsin	de
dc.subject.eng	tomography	de
dc.subject.eng	ABR	de
dc.subject.eng	auditory brainstem response	de
dc.subject.eng	multichannel	de
dc.subject.eng	optrode	de
dc.identifier.urn	urn:nbn:de:gbv:7-11858/00-1735-0000-002E-E55A-2-0
dc.affiliation.institute	Göttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB)	de
dc.subject.gokfull	Biologie (PPN619462639)	de
dc.description.embargoed	2019-12-15
dc.identifier.ppn	1046408259

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Beschreibung:: Dissertation

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GGNB - Göttinger Graduiertenzentrum für Neurowissenschaften, Biophysik und molekulare Biowissenschaften [1116]
GGNB - Göttingen Graduate Center for Neurosciences, Biophysics and Molecular Biosciences

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