Abstract Otology 2000 D03-1

Alan F. Ryan MD (1), Elmar Oestreicher MD (2), Yehoash Raphael PhD (3), Jukka Ylikoski MD (4), Justin Weir MD (5)

(1) Div. of Otolaryngology UCSD School of Medicine USA-La Jolla CA
(2) ENT Department Technical University of Munich D-München
(3) Kresge Hearing Research Institute The Univ.of Michigan Medical School MSRB III Room-9303 USA-Ann Arbor, MI
(4) Department of Otorhinolaryngology Helsinki University CentralHospital SF-Helsinki
(5) Physiology University of Bristol GB-Bristol

Sensorineural hearing loss consists of damage to the hair cells and neurons of the cochlea. Until recently, the mechanisms responsible for such damage were unknown. Moreover, options for the prevention and treatment of sensorineural hearing loss and peripheral vestibular disorders were limited. Recently, application of the techniques of cellular and molecular biology to the inner ear have begun to provide new information on these topics. Molecular signals which control the development of inner ear hair cells and neurons are being discovered, and could be applied to the regeneration of sensory structures. Intracellular events that lead to cell damage and death in the inner ear, and pharmacological mechanisms for prevention, have been identified. Using the tools and findings of molecular biology, methods for the application of gene therapy to the inner ear have been explored. Techniques for transplantation of sensory cells are also being developed. The participants in the round table will review recent developments, and discuss the potential for future application to patients.

Abstract Otology 2000 D03-2

Elmar Oestreicher MD, Wolfgang Arnold MD, Dominik Felix MD

ENT Department Technical University of Munich D-München

The cochlear inner hair cells (IHC) are connected to afferent type I auditory neurons and use probably L-glutamate as a neurotransmitter. This inner hair cell synapse receives efferent input from the lateral part of the efferent olivo-cochlear system with neurons originating in the brainstem and terminating below IHC synapsing with the afferent type I dendrites. A number of substances have been proposed to function as neurotransmitter or neuromodulator in the lateral efferent system: acetylcholine, GABA, dopamine, enkephaline and dynorphine. With the aid of microiontophoretic techniques we studied several transmitter candidates and characterized their receptor subtypes as well as their function on spontaneous or evoked activity of afferent dendrites. The results showed that the glutamatergic transmission of IHC is facilitated by all types of glutamate receptors: ionotropic glutamate receptors of the NMDA and AMPA type as well as group I and II metabotropic glutamate receptors. This excitatory glutamatergic transmission is under inhibitory control of GABA (mediated by GABA A receptors) and dopamine (mediated by D1 and D2 receptors). In contrast, acetylcholine was able to excite afferent dendrites via muscarinic receptors. These results demonstrate that the lateral efferent system has modulatory function on the glutamatergic neurotransmission of IHC. Excitation of afferent dendrites by glutamate released from IHC can thus be tuned in different physiologic or pathophysiologic conditions. During over-excitation of IHC like in noise, a possible therapy based on the neurochemical data would be a) glutamate release inhibitors b) glutamate antagonists c) dopamine agonists d) GABA agonists or a combination from a,b and c,d.