Cholinergic antagonists block contralateral suppression of distortion product otoacoustic emissions.
AuthorKujawa, Sharon Guilds.
Committee ChairGlattke, Theodore J.
MetadataShow full item record
PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
AbstractPresentation of an acoustic signal to one ear can suppress sound-evoked activity recorded at the opposite ear. The suppression appears to be mediated by uncrossed medial olivocochlear (MOC) efferent neurons synapsing with cochlear outer hair cells (OHCs). The cellular and molecular mechanisms underlying this response suppression remain unclear. Recent investigations suggest that the mechanism involves an altered mechanical response of the cochlear partition produced by the MOC neurostransmitter, acetylcholine (ACh), acting on the OHCs. The cholinergic receptor subtypes mediating this efferent control remain unclear. The purpose of this investigation was to provide in vivo pharmacologic characterization of one efferent-mediated response: the contralateral sound suppression of distortion product otoacoustic emissions (DPOAEs). Urethane-anesthetized guinea pigs were used. Perilymph spaces of ipsilateral cochleae were perfused with artificial perilymph (control) and increasing concentrations of nicotinic or muscarinic receptor antagonists or strychnine, a known blocker of MOC activity. Experimental drugs were washed from cochlear perilymph spaces with artificial perilymph. Perfusates were introduced at 2.5 μl/min for 10 min. After each period of perfusion, DPOAEs were recorded before, during and after contralateral wideband noise (WBN) stimulation (70 dB SPL). Pre-perfusion, contralateral WBN attenuated ipsilateral DPOAEs between 1-4 dB. This suppression was blocked dose-responsively by a wide variety of nicotinic and muscarinic receptor antagonists. Strychnine and the nicotinic antagonists alpha-bungarotoxin, kappa-bungarotoxin and curare blocked contralateral suppression at nanomolar concentrations and demonstrated similar potencies. These findings support the hypothesis that a novel nicotinic receptor mediates efferent-induced suppression of DPOAEs. Of the muscarinic antagonists tested (pirenzepine, AF-DX 116, 4-DAMP, atropine), 4-DAMP demonstrated the most potent blockade of contralateral suppression, suggesting either that this efferent control also can be mediated by an M₃ muscarinic receptor, or that the putative novel nicotinic receptor also is blocked by low concentrations of this muscarinic receptor antagonist. Effects were largely reversible and selective to the synapse under study. Furthermore, suppression was not altered by repeated perfusions of the control solution alone. These results provide the first comprehensive, in vivo characterization of cholinergic receptors mediating suppressive effects of efferent activation at the MOC-OHC synapse.
Degree ProgramSpeech and Hearing Sciences