We have isolated, for the first time, individual efferent nerve terminals from the base of cochlear outer hair cells and propose to investigate several fundamental processes involved in the release of neurotransmitter from these terminals. An hypothesis of efferent function is put forward which is compatible with their purported role in protecting the sensory cells from acoustic trauma. Ionic currents involved in neurotransmission will be identified by the whole-cell patch clamp technique, their activation by electrical and chemical means studied, and their modulation by putative autoreceptors determined. Measurements of plasma membrane capacitance will be used to monitor changes in membrane area as an assay for the fusion events thought to occur during transmitter release. Optical techniques will be applied to investigate the role of cytosolic calcium in release of neurotransmitter and to determine whether adenosine triphosphate, a putative cotransporter, is released from these terminals. Results of all of these investigations will be correlated with the longitudinal position of origin of the nerve terminals since it is known from histochemical data that there is a graded distribution of cholinergic and GABAergic fibers within the cochlea. These data will be used to support or refute standing hypotheses of the role of the medial efferent nerves in the process of hearing.

Project Start
Project End
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
14
Fiscal Year
1998
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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