The ontogenetic mechanisms that are responsible for the adult patterns of innervation and function within the mammalian cochlea are poorly understood. The goal of this application is to investigate the mechanisms which underlie efferent synaptogenesis, specifically, the development of olivocochlear (OC) synapses. An additional goal is to test the generality of current models of synaptogenesis and competition in the maturation of the OC system, and ultimately, of auditory function. Since OC neurons demonstrate best frequency responses, are involved with the detection of signals in noise, and appear morphologically mature before the onset of hearing, understanding their development may help us to understand hearing and disorders associated with hearing in preterm and newborn infants.
The specific aims are to test the following hypothesis: 1) medial OC neurons exhibit a developmental waiting period, that is, they send projections to the cochlea that synapse on intermediate targets, 2) medial OC neurons are capable of releasing acetylcholine prior to synapsing on outer hair cells, and 3) lateral OC neurons undergo a separate period of cochlear synaptogenesis from medial OC neurons. These investigations focus primarily on the first postnatal week in newborn hamsters and gerbils and include a variety of approaches such as: retrograde and anterograde labeling to visualize the temporal sequence of efferent projections as well as synaptic input to the efferent neurons; serial-section electron microscopy of labeled efferent terminals; histochemical, immunochemical, and in situ hybridization studies of the expression of neurotransmitters and developmental markers; and characterization of enzyme activity to assess neurotransmitter mechanisms. Importantly, this research should generate specific models that can be tested by experimental interventions.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC004086-04
Application #
6379479
Study Section
Hearing Research Study Section (HAR)
Program Officer
Freeman, Nancy
Project Start
1998-08-01
Project End
2003-07-31
Budget Start
2001-08-01
Budget End
2002-07-31
Support Year
4
Fiscal Year
2001
Total Cost
$371,296
Indirect Cost
Name
Central Institute for the Deaf
Department
Type
DUNS #
City
Saint Louis
State
MO
Country
United States
Zip Code
63110
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Tong, Benton; Hornak, Aubrey J; Maison, Stéphane F et al. (2016) Oncomodulin, an EF-Hand Ca2+ Buffer, Is Critical for Maintaining Cochlear Function in Mice. J Neurosci 36:1631-5
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Simmons, Dwayne D; Tong, Benton; Schrader, Angela D et al. (2010) Oncomodulin identifies different hair cell types in the mammalian inner ear. J Comp Neurol 518:3785-802
Fu, Benjamin; Le Prell, Colleen; Simmons, Dwayne et al. (2010) Age-related synaptic loss of the medial olivocochlear efferent innervation. Mol Neurodegener 5:53
Osman, Abdullah A; Schrader, Angela D; Hawkes, Aubrey J et al. (2008) Muscle-like nicotinic receptor accessory molecules in sensory hair cells of the inner ear. Mol Cell Neurosci 38:153-69
Gagnon, Patricia M; Simmons, Dwayne D; Bao, Jianxin et al. (2007) Temporal and genetic influences on protection against noise-induced hearing loss by hypoxic preconditioning in mice. Hear Res 226:79-91

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