Early stages of neural processing are informed by later stages, and this descending control plays multiple, important roles. Among sensory systems, descending control in the auditory system is probably most complex, and therefore least understood. The olivocochlear efferent system is a reflex pathway that modifies the response of the organ of Corti to acoustic signals. Here we focus on the medial olivocochlear system (MOC), which through a sophisticated cholinergic mechanism protects against acoustic damage and enhances the ability of the cochlea to detect signals in noise. MOC cells receive glutamatergic reflex input from cochlear nucleus but also descending input from cortex and midbrain. Moreover, MOC neurons excited by acetylcholine receptor agonists suggesting local cholinergic influences. How these distinct inputs function relative to one another is unknown. Indeed, the literature has not clarified functional differences in these inputs because of limitations in the classical physiological or anatomical approaches to independently activate different neural pathways to the MOC neurons. Here we propose to use modern mouse genetic and optogenetic techniques combined with electrophysiology in a brain slice system to determine the intrinsic and synaptic properties that underlie olivocochlear function. An additional point of control of MOC system is through MOC collaterals made in the cochlear nucleus, which ultimately feeds back to MOC cells. How cholinergic signaling from MOC and from midbrain pedunculopontine tegmental controls the MOC is unknown. A working hypothesis is that MOC and PPT act on distinct microcircuits in cochlear nucleus and that this translates to differential feedback control to MOC via the IC. This will be tested here using electrophysiological and optogenetic analysis of cholinergic influences in the cochlear nucleus in vitro and in vivo. Because the MOC system plays an essential in protection against noise damage, it is likely that the results of this study will lead to a better means to prevent damage to, or recover, human hearing.

Public Health Relevance

This study will examine functional aspects of the brain circuitry underlying the cochlear efferent system, a mechanism that the brain uses to protect the ear against noise damage. Electrophysiological, genetic and optogenetic techniques will be combined to analyze this neural circuitry at an unprecedented level of resolution. The results should be applicable in the development of means to correct hearing loss in humans.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC004450-22
Application #
9985098
Study Section
Auditory System Study Section (AUD)
Program Officer
Cyr, Janet
Project Start
1999-09-01
Project End
2023-08-31
Budget Start
2020-09-01
Budget End
2021-08-31
Support Year
22
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
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Tang, Zheng-Quan; Trussell, Laurence O (2017) Serotonergic Modulation of Sensory Representation in a Central Multisensory Circuit Is Pathway Specific. Cell Rep 20:1844-1854
Moore, Lucille A; Trussell, Laurence O (2017) Corelease of Inhibitory Neurotransmitters in the Mouse Auditory Midbrain. J Neurosci 37:9453-9464
Yaeger, Daniel B; Trussell, Laurence O (2016) Auditory Golgi cells are interconnected predominantly by electrical synapses. J Neurophysiol 116:540-51
Lu, Hsin-Wei; Trussell, Laurence O (2016) Spontaneous Activity Defines Effective Convergence Ratios in an Inhibitory Circuit. J Neurosci 36:3268-80
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Yaeger, Daniel B; Trussell, Laurence O (2015) Single granule cells excite Golgi cells and evoke feedback inhibition in the cochlear nucleus. J Neurosci 35:4741-50

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