VESTIBULAR EFFERENT CELL AND MOLECULAR BIOLOGY

  • Spiegel, Allen M. (PI)
  • Wackym, P. Ashley (PI)
  • Morell, Robert (PI)
  • Dibello, Paul (PI)
  • Wackym, P. Ashley (PI)

Project: Research project

Description

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.
StatusActive
Effective start/end date7/1/91 → …

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

Fingerprint

Multiple Endocrine Neoplasia Type 1
National Human Genome Research Institute (U.S.)
Genes
Proteins
Drosophila
National Institute of Diabetes and Digestive and Kidney Diseases (U.S.)
Protein Interaction Domains and Motifs
Yeasts
Neoplasms
Germ-Line Mutation
Hyperparathyroidism
X Ray Crystallography
Drosophila Proteins
Hypercalcemia
Missense Mutation
Tumor Suppressor Genes
Islets of Langerhans
Immunoprecipitation
Immunoblotting
Mutagenesis

ASJC

  • Medicine(all)
  • Neuroscience(all)