The proposed studies are a logical continuation of previous work by these investigators which have sought to identify and characterize transmitter/modulators of the vestibular periphery. The present proposal will focus specifically on acetylcholine (ACh) receptor subtypes. The questions to be addressed are: 1) What are the characteristics of the ACh receptors involved?; 2) What are the interactions between ACh and other transmitters and modulators?; 3) How do interactions between these agents influence vestibular physiology?; 4) Is there a correlation between hair cells shape and/or placement (location) in the vestibular organ and the nature of that hair cells response to ACh? A number of methods will be used to record bioelectric activity from the semi-circular canals and compare these with responses from the saccule. Bioelectric activity will be recorded using voltage and current clamping of hair cells isolated from the saccule and the semicircular canals. In addition to recording techniques, in situ hybridization and immunocytochemistry will be used to characterize and hopefully identify the location of the different ACh receptors and their subunits. The identity and distribution of other receptors will be mapped using these same techniques. A new preparation employing slices of semicircular canals (ampullae) will be used to study hair cells in situ. This technique in addition to the previously utilized techniques will be used to compare responses to ACh related compounds and other selective ligands. Thus these studies will use identification techniques of immunocytochemistry and in situ hybridization in conjunction with physiology and pharmacology to assess the functional role of acetylcholine and other neurotransmitter/modulators of the vestibular periphery. These studies have practical health related implications in terms of the future development of vestibular suppressants for treatment of vestibular pathologies and motion sickness. A clear understanding of the agents involved in normal vestibular function may lead to the development of a practical and safe vestibular suppressant. Also, while vestibular physiology is of interest in its own right, the process of the vestibular periphery are sufficiently similar to those of a cochlea that knowledge gained may be applied to hearing disorders.
| Guth, P S; Perin, P; Norris, C H et al. (1998) The vestibular hair cells: post-transductional signal processing. Prog Neurobiol 54:193-247 |
| Ricci, A; Norris, C; Guth, P (1991) Cyclic AMP modulates sensory-neural communication at the vestibular end organ. Brain Res 565:78-84 |
