This project aims to understand the functions and actions of descending neural systems to the cochlea and cochlear nucleus. A particular focus is the olivocochlear (OC) neurons, which are divided into medial (MOC) and lateral (LOC) subgroups. These neurons project from the superior olivary complex to the cochlea, with MOC endings formed on outer hair cells and LOC endings formed mainly on the dendrites of auditory-nerve fibers beneath inner hair cells. We will study, in Aim 1A, MOC actions on outer hair cells using otoacoustic emission tests, to gain insight into parallel results in humans. The results will allow us to infer the physiological and anatomical characteristics of human MOC neurons. Using recordings and labeling of MOC single units, we will study, in Aim 1B, the characteristics of MOC Contra units, which respond to sound in the ear contralateral to the one that receives their axonal projections. These results will give us insight as to how the MOC contralateral reflex differs from that to ipsilateral sound. We will study, in Aim 1C, the MOC innervation of the human cochlea.
This aim has particular relevance for interpretation of human otoacoustic emission tests, and it is made possible by recent advances that allow us to remove the embedding medium, celloidin, from human sections and then immunostain them. We will, in Aim 2A, use new techniques and an assay that allows us to observe small, potentially LOC-induced changes on auditory-nerve response following reversible hearing loss where we can measure responses on the previously plugged ipsilateral side. We will, in Aim 2B, use a new mouse strain, ChAT-cre driving tdTomato to visualize neural inputs to LOC dendrites. These data will allow us to specify the inputs to LOC neurons, much as we have done for MOC neurons and motoneurons of the middle ear muscles in the previous grant period. With this knowledge, we will better know the neural mechanisms of the olivocochlear neurons and how they function to provide protection, reduce masking, and provide other functions relevant to the workplace and to everyday life.

Public Health Relevance

This project aims to understand the functions and actions of descending neural systems to the cochlea and cochlear nucleus. A particular focus is the olivocochlear (OC) neurons, which are divided into medial (MOC) and lateral (LOC) subgroups. We will study MOC actions on outer hair cells using otoacoustic emission tests, MOC unit responses and projections with recording and labeling, and the MOC innervation of the human cochlea using immunostaining. We will study LOC effects using responses of the auditory nerve in models of unilateral hearing loss and LOC inputs using tracers and new strains of mice. The results should give us valuable information about how these neurons provide important functions like protecting the ear from damage due to high-level sound and reducing the effects of noise masking.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC001089-24
Application #
9097689
Study Section
Auditory System Study Section (AUD)
Program Officer
Platt, Christopher
Project Start
1991-06-01
Project End
2020-06-30
Budget Start
2016-07-01
Budget End
2017-06-30
Support Year
24
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Massachusetts Eye and Ear Infirmary
Department
Type
DUNS #
073825945
City
Boston
State
MA
Country
United States
Zip Code
Guinan Jr, John J (2018) Olivocochlear efferents: Their action, effects, measurement and uses, and the impact of the new conception of cochlear mechanical responses. Hear Res 362:38-47
Barber, Samuel R; Kozin, Elliott D; Remenschneider, Aaron K et al. (2017) Auditory Brainstem Implant Array Position Varies Widely Among Adult and Pediatric Patients and Is Associated With Perception. Ear Hear 38:e343-e351
Brown, M Christian (2016) Recording and labeling at a site along the cochlea shows alignment of medial olivocochlear and auditory nerve tonotopic mappings. J Neurophysiol 115:1644-53
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Hight, Ariel Edward; Kozin, Elliott D; Darrow, Keith et al. (2015) Superior temporal resolution of Chronos versus channelrhodopsin-2 in an optogenetic model of the auditory brainstem implant. Hear Res 322:235-41
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Verma, Rohit U; Guex, Amélie A; Hancock, Kenneth E et al. (2014) Auditory responses to electric and infrared neural stimulation of the rat cochlear nucleus. Hear Res 310:69-75
Brown, M Christian (2014) Single-unit labeling of medial olivocochlear neurons: the cochlear frequency map for efferent axons. J Neurophysiol 111:2177-86

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