Transduction of acoustic stimuli into neural signals occurs in the complicated mechanical system of the organ of Corti. The frequency selectivity of a hair cell is provided by mechanical tuning in which the strength of coupling between the hair cell and tectorial membrane plays an important role. An alteration of this coupling should cause, in addition to other disorders in hearing, increase in the noise of the system which may be received as tennitus. Mechanical properties of hair cell cilia and tectorial membrane are highly dependent on calcium concentration in such a manner that a decrease in intracochlear calcium concentration will cause a decrease in coupling between the hair cells and tectorial membrane. Furthermore, it is known that salicylates in doses capable of evoking tinnitus in humans will decrease free calcium in serum, our preliminary data in rats showing a decrease of calcium in cerebrospinal fluid (CSF) and perilymph as well. We hypothesize that some forms of tinnitus may result from a decrease of intrachoclear calcium concentration causing decoupling of the hair cell connections to the tectorial membrane and altering the mechanical coupling of cilia to hair cells as well. This hypothesis will be investigated from three different perspectives. One deals with the extent and time course of calcium flux in serum. CSF and perilymph produced by salicylate administration and the possibility of preventing a drop in calcium concentration by sequential administration of calcium gluconate. The second is to test close-to-threshold characteristics of cochlear microphonics and N1 potentials, correlating these changes with calcium levels. The third is directed toward testing changes in the spontaneous activity of single neurons in the inferior colliculus in the experimental situations described above. This allows for detection of changes in spontaneous activity which may be related to a tinnitus-like phenomenon. It is hoped that data obtained from this study may provide a better understanding of tinnitus generation, thus aiding in the creation of an animal model for tinnitus, as well as providing a possible new approach for the treatment of tinnitus and related auditory disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS022024-01
Application #
3403879
Study Section
Hearing Research Study Section (HAR)
Project Start
1985-04-01
Project End
1988-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
Jastreboff, P J; Brennan, J F; Coleman, J K et al. (1988) Phantom auditory sensation in rats: an animal model for tinnitus. Behav Neurosci 102:811-22
Jastreboff, P J; Brennan, J F; Sasaki, C T (1988) An animal model for tinnitus. Laryngoscope 98:280-6
Jastreboff, P J; Issing, W; Brennan, J F et al. (1988) Pigmentation, anesthesia, behavioral factors, and salicylate uptake. Arch Otolaryngol Head Neck Surg 114:186-91
Jastreboff, P J; Hansen, R; Sasaki, P G et al. (1986) Differential uptake of salicylate in serum, cerebrospinal fluid, and perilymph. Arch Otolaryngol Head Neck Surg 112:1050-3
Jastreboff, P J; Sasaki, C T (1986) Salicylate-induced changes in spontaneous activity of single units in the inferior colliculus of the guinea pig. J Acoust Soc Am 80:1384-91