The Role of Hair Cell-Based Activity in Auditory Nerve Myelination – UROP Spring Symposium 2023

The Role of Hair Cell-Based Activity in Auditory Nerve Myelination

Stella Mulrenin

Stella Mulrenin photo

Pronouns: she/her

Research Mentor(s): David Kohrman
Research Mentor School/College/Department: Otolaryngology/Human Genetics / Medicine
Program: UROPF
Session: Session 2 (10:00am – 10:50am)
Authors: David Kohrman, Stella Mulrenin, Emma Sycko

Abstract

Myelination of neurons is important for conduction of action potential in neurons and thus allowing for motor and sensory function. While neuronal activity and experience is known to regulate myelination in the central nervous system, little is understood about how these processes impact myelin in peripheral nerves. We will test whether hair cell-dependent neuronal activity regulates myelin development on the peripheral portion of the auditory nerve (AN), a set of sensory neurons that transmit sound information from the cochlea to the central auditory system. Tmie and Vglut3 mice carry mutant genes that disrupt mechanotransduction and synaptic function in sensory hair cells in the cochlea and thus alter AN activity. To study these mice, we track mutant gene status using PCR-based genotyping. The cochleae of mutants and controls are then dissected at postnatal day 12 or 21, stained with myelin-related antibodies as well as a nuclear marker, then imaged by confocal microscopy. Software analyses are used to quantify AN myelin nodal structures (ANKG and CASPR proteins) and myelin basic protein expression at a range of frequency positions along each cochlea. Results thus far support the prediction that altered AN activity in Tmie and Vglut3 mutants is associated with abnormal AN myelination. We are also using genetic approaches to study a potential requirement for sensory hair cells on AN health after experimentally induced demyelination in the cochlea. Preliminary results suggest that functioning hair cells are necessary to prevent loss of AN fibers following injury of myelinating Schwann cells. These studies should help us to better understand mechanisms that control normal myelin development and novel ways to treat humans suffering from myelin disorders and hearing loss.

Life Science

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