The focus of this project will be on the cellular and molecular basis of vestibular function, e.g., neural transduction and modulation, by the identification and subcellular localization of afferent and efferent neurotransmitter and receptors. The experiments proposed herein will examine the location of somata and the pattern of innervation of the efferent neurons to the vestibular receptors in the chinchilla. The experiments will test the hypothesis that calcitonin gene-related peptide (CGRP) may be used as a specific marker for efferent neurons innervating the vestibular neuroepithelium. The molecular basis of efferent neuron function will be investigated using receptor binding, immunohistochemistry, immunoelectron microscopy, and in situ hybridization histochemistry. The guiding hypothesis is that CGRP-immunoreactive efferent terminals, that co- contain acetylcholine, appose postsynaptic CGRP receptors and nicotinic acetylcholine receptors in primary afferent terminals and hair cells. The proposed experiments are designed to being answering the questions that resulted from the preliminary work completed during my postdoctoral year in the Department of Anatomy and Cell Biology at UCLA. The collaborative relationship that developed with Dr. Paul Micevych at UCLA will continue during the proposed project. Besides the experimental projects planned, the need exists to apply molecular biology techniques to the study of human pathological material, taken at operation or post-mortem. The Principal Investigator will be taught the knowledge and skills necessary to collect and process human inner ear tissues for this purpose by Professor Ugo Fisch and Dr. Heidi Felix of the University of Zurich. Human inner ear tissue collected in Zurich will be used to validate the chinchilla animal model of vestibular efferent/afferent interaction. The information and skills to be obtained from this five year training period will provide: (1) the basis for an experimental model of vestibular efferent/afferent interaction, and (2) a means to understand and study, at the molecular level, the underlying defects in patients with vestibular disorders, such as viral labyrinthitis, Meniere's disease, benign positional vertigo and peripheral vestibulopathy secondary to ototoxicity.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08DC000062-04
Application #
2124335
Study Section
Communication Disorders Review Committee (CDRC)
Project Start
1991-07-01
Project End
1995-03-31
Budget Start
1994-07-01
Budget End
1995-03-31
Support Year
4
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Surgery
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Wackym, P A; Chen, C T; Ishiyama, A et al. (1996) Muscarinic acetylcholine receptor subtype mRNAs in the human and rat vestibular periphery. Cell Biol Int 20:187-92
Bridgeman, D; Hoffman, L; Wackym, P A et al. (1996) Distribution of choline acetyltransferase mRNA in the efferent vestibular neurons of the chinchilla. J Vestib Res 6:203-12
Wackym, P A; Popper, P; Ward, P H et al. (1991) Cell and molecular anatomy of nicotinic acetylcholine receptor subunits and calcitonin gene-related peptide in the rat vestibular system. Otolaryngol Head Neck Surg 105:493-510