The Journal of Neurophysiology Vol. 88 No. 2 August 2002, pp. 699-714
Copyright ©2002 by the American Physiological Society

Cisplatin-Induced Hyperactivity in the Dorsal Cochlear Nucleus and Its Relation to Outer Hair Cell Loss: Relevance to Tinnitus

Department of Otolaryngology, Wayne State University School of Medicine, Detroit, Michigan 48201

Kaltenbach, James A., John D. Rachel, T. Alecia Mathog, Jinsheng Zhang, Pamela R. Falzarano, and Matthew Lewandowski. Cisplatin-Induced Hyperactivity in the Dorsal Cochlear Nucleus and Its Relation to Outer Hair Cell Loss: Relevance to Tinnitus. J. Neurophysiol. 88: 699-714, 2002. Cisplatin causes both acute and chronic forms of tinnitus as well as increases in spontaneous neural activity (hyperactivity) in the dorsal cochlear nucleus (DCN) of hamsters. It has been hypothesized that the induction of hyperactivity in the DCN may be a consequence of cisplatin's effects on cochlear outer hair cells (OHCs); however, systematic studies testing this hypothesis have yet to appear in the literature. In the present investigation, the relationship between hyperactivity and OHC loss, induced by cisplatin, was examined in detail. Hamsters received five treatments of cisplatin at doses ranging from 1.5 to 3 mg · kg¹ · day¹, every other day. Beginning 1 mo after initiation of treatment, electrophysiological recordings were carried out on the surface of the DCN to measure spontaneous multiunit activity along a set of coordinates spanning the medial-lateral (tonotopic) axis of the DCN. After recordings, cochleas were removed and studied histologically using a scanning electron microscope. The results revealed that cisplatin-treated animals with little or no loss of OHCs displayed levels of activity similar to those seen in saline-treated controls. In contrast, the majority (75%) of cisplatin-treated animals with severe OHC loss displayed well-developed hyperactivity in the DCN. The induced hyperactivity was seen mainly in the medial (high-frequency) half of the DCN of treated animals. This pattern was consistent with the observation that OHC loss was distributed mainly in the basal half of the cochlea. In several of the animals with severe OHC loss and hyperactivity, there was no significant damage to IHC stereocilia nor any observable irregularities of the reticular lamina that might have interfered with normal IHC function. Hyperactivity was also observed in the DCN of animals showing severe losses of OHCs accompanied by damage to IHCs, although the degree of hyperactivity in these animals was less than in animals with severe OHC loss but intact IHCs. These results support the view that loss of OHC function may be a trigger of tinnitus-related hyperactivity in the DCN and suggest that this hyperactivity may be somewhat offset by damage to IHCs.