In this project, the role of the olivocochlear bundle (OCB) will be explored in multiple studies of peripheral auditory development. The finding the peripheral auditory function in animals reared in the absence of the OCB is decidedly pathological suggests that the OCB plays a role in cochlear development. However, an alternative possibility is that animals that lose their OCB early in life are highly susceptible to acoustic trauma. In proposed experiments, the peripheral auditory consequences of rearing animals deefferented at birth in a quiet environment will be studied, in addition to deefferented animals exposed to noise in an attempt to determine the source of the cochlear pathology associated with OCB transection. Auditory nerve pathology produced by such lesions is consistent with the malfunction, or abnormal expression, of the cochlear amplifier. Auditory nerve fibers from adults deefferented at birth exhibit elevated thresholds, relatively broad tuning, low spontaneous discharge rages and poor tip-totail rations. Peripheral auditory nonlinearity in animals lesioned as neonates will be assessed to test the hypothesis that OCB interactions with outer hair cells (OHCs) are required for the normal expression of active hypothesis that OCB interactions with outer hair cells (OHCs) are required for the normal expression of active cochlear mechanics. A separate experiment will test the hypothesis that the OCB plays a role in the refinement of exuberant synapses between inner hair cells and auditory nerve dendrites that occurs during development. While the proposed experiments will focus primarily on peripheral auditory pathology generated by early deefferentation, OCB development, per se, will continue to be explored. This will be done by determining the role of OHCs in the OCB-IHC detachment and intracochlear migration dynamic that occurs early in feline life, by destroying OHCs prior to the onset of hearing and anatomically evaluating the disposition of OCB terminals within the organ of Corti in physiologically characterized animals. Finally, the gap in our understanding of structure/function aspects of OCB development will be filled by studying its cochlear innervation histologically and ultrastructurally in physiologically characterized animals.

Project Start
1999-02-01
Project End
2000-01-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
15
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Father Flanagan's Boys' Home
Department
Type
DUNS #
City
Boys Town
State
NE
Country
United States
Zip Code
68010
Yang, Tian; Jia, Zhonglin; Bryant-Pike, Whitney et al. (2014) Analysis of PRICKLE1 in human cleft palate and mouse development demonstrates rare and common variants involved in human malformations. Mol Genet Genomic Med 2:138-51
Fritzsch, Bernd; Tessarollo, Lino; Coppola, Enzo et al. (2004) Neurotrophins in the ear: their roles in sensory neuron survival and fiber guidance. Prog Brain Res 146:265-78
Cohn, Edward; Bhattacharya, Gautam; Pearsall, Nicole et al. (2004) Immunohistochemistry and reverse transcriptase-polymerase chain reaction as methods for diagnostic determination of usher syndrome type IIa. Laryngoscope 114:1310-4
Maklad, Adel; Fritzsch, Bernd (2003) Development of vestibular afferent projections into the hindbrain and their central targets. Brain Res Bull 60:497-510
Fritzsch, Bernd (2003) Development of inner ear afferent connections: forming primary neurons and connecting them to the developing sensory epithelia. Brain Res Bull 60:423-33
Maklad, Adel; Fritzsch, Bernd (2003) Partial segregation of posterior crista and saccular fibers to the nodulus and uvula of the cerebellum in mice, and its development. Brain Res Dev Brain Res 140:223-36
Xiang, Mengqing; Maklad, Adel; Pirvola, Ulla et al. (2003) Brn3c null mutant mice show long-term, incomplete retention of some afferent inner ear innervation. BMC Neurosci 4:2
Maklad, Adel; Fritzsch, Bernd (2002) The developmental segregation of posterior crista and saccular vestibular fibers in mice: a carbocyanine tracer study using confocal microscopy. Brain Res Dev Brain Res 135:1-17
Fritzsch, B; Beisel, K W; Jones, K et al. (2002) Development and evolution of inner ear sensory epithelia and their innervation. J Neurobiol 53:143-56
Judice, Tiffany N; Nelson, Nathan C; Beisel, Chase L et al. (2002) Cochlear whole mount in situ hybridization: identification of longitudinal and radial gradients. Brain Res Brain Res Protoc 9:65-76

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