The olivocochlear bundle (OCB) consists of lateral efferent fibers that innervate afferent dendrites beneath inner hair cells (IHCs), and medial efferent fibers that innervate outer hair cells (OHCs) directly. A great deal is known about the hair cells and their fate following acoustic over- stimulation and exposure to ototoxic drugs and how their loss influences basic auditory function. By contrast, little is known about the possible contributions made by OCB to either normal cochlear function or to susceptibility to cochlear damage, and what little is known is primarily based on studies of the medial efferent system only. The primary goals of this project are to examine lateral and medial efferent influences on (a) suprathreshold auditory function and individual susceptibility to damage; (b) hair cell loss and threshold shifts caused by noise and three ototoxic drugs that differ in their site of action within the cochlea (kainic acid, a glutamate analogues that temporarily disrupts IHC/afferent fiber synapse; kanamycin, a aminoglycoside that destroys OHCs; and carboplatin, and antineoplastic agent that selectively destroys IHCs in the chinchilla cochlea); and (3) recovery of IHC/afferent fiber synapses after kainate- induced excitotoxic damage. The experiments proposed are logical outgrowths of our previous studies of OCB involvement in "toughening" and noise-induced hearing loss, and of kainic acid excitotoxicity. Physiological measures will be obtained from awake animals before and after complete transection of the inferior vestibular nerve as it enters the internal auditory meatus. Physiological measures will include tests of cochlear non-linearity, frequency resolution, and temporal resolution, performed in quiet and in the presence of making noise. In a subset of experiments, chronic infusion of strychnine will be used to disable the medial efferent system, to separate our medial from lateral efferent effects. The results will provide important information regarding the role of the OCB in susceptibility to cochlear damage caused by noise and ototoxic drugs, as well as its role in normal auditory function.
NIH ExPorter
NIH ExPorter