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Investigating approaches for selective modulation of LOC efferent input to the cochlea

Khalil, Mahmoud (2024) Investigating approaches for selective modulation of LOC efferent input to the cochlea. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

The lateral olivocochlear pathway (LOC) is an efferent pathway that originates from the lateral superior olivary complex and directly innervates the dendrites of auditory nerve fibers beneath inner hair cells. Investigating the LOC pathway has been difficult due to the lack of tools that would allow for direct and specific manipulation of the LOC pathway. In chapter 2 of my thesis, I explore the use of retrograde Adeno-Associated viruses (AAVs) for inner ear gene delivery to LOC neurons and report on the remarkable ability of the AAV2-retro serotype to spread throughout the central nervous system and onto the contralateral cochlea when it is unilaterally delivered to the inner ear. In chapter 3 I characterize a novel mouse line, X-Cre, that would allow for the selective manipulation of the LOC pathway. In chapters 4 and 5 I attempt to utilize the X-Cre mouse line to investigate its function during development and to investigate its modulation of auditory nerve activity in adult animals. Throughout both chapters, however, I encounter unforeseen issues that limit the specificity of the X-Cre mouse line to the LOC pathway. In chapter 6 I discuss potential approaches to restricting transgene expression in the X-Cre mouse line to the LOC pathway as well as alternative approaches for specific targeting of the LOC pathway beyond the use of the X-Cre mouse line.

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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Khalil, MahmoudMAK429@pitt.eduMAK429
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairCheetham, Clairecheetham@pitt.edu
Committee MemberRunyan, Carolinerunyan@pitt.edu
Committee MemberSadagopan, Srivatsunvatsun@pitt.edu
Committee MemberSeal, Rebeccarpseal@pitt.edu
Committee MemberLu, Yongylu@neomed.edu
Thesis AdvisorKandler, Karlkkarl@pitt.edu
Date: 14 October 2024
Date Type: Publication
Defense Date: 23 July 2024
Approval Date: 14 October 2024
Submission Date: 13 August 2024
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 184
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Neurobiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: lateral olivocochlear pathway LOC AAV Gene therapy efferent innervation efferent feedback auditory inner ear injection Adeno-Associated Virus Transgenic mouse line BAC Transgenesis Transposase Transgenesis
Date Deposited: 14 Oct 2024 16:05
Last Modified: 14 Oct 2024 16:05
URI: http://d-scholarship.pitt.edu/id/eprint/46924

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