J Comp Physiol A (1994) 174:351-369 dleumal of Newel, and Rheldolelw A 9 Springer-Verlag 1994 Discharge patterns of chicken cochlear ganglion neurons following kanamycin-induced hair cell loss and regeneration R.J. Salvi, S.S. Saunders, E. Hashino, L. Chen Hearing Research Laboratory, Department of Communicative Disorders & Sciences, 215 Parker Hall, State University of New York at Buffalo,Buffalo,NY 14214, USA Accepted: 4 October 1993 Abstract. Hair cells in the basal, high frequency region (> 1100 Hz) of the chicken cochlea were destroyed with kanamycin (400 mg/kg/d x 10 d) and allowed to regen- erate. Afterwards, single unit recordings were made from cochlear ganglion neurons at various times post-treat- ment. During the first few weeks post-treatment, only neurons with low characteristic frequencies (< 1100 Hz) responded to sound. Despite the fact that the low fre- quency region of the cochlea was not destroyed, neurons with low characteristic frequencies had elevated thresholds, abnormally broad U-shaped or W-shaped tuning curves and low spontaneous discharge rates. At 2 days post-treatment, the spontaneous discharge rates of some acoustically unresponsive units fluctuated in a rhythmical manner. As recovery time increased, thresholds decreased, tuning curves narrowed and devel- oped a symmetrical V-shape, spontaneous rate increased and neurons with higher characteristic frequencies began to respond to sound. In addition, the proportion of inter- spike interval histograms with regularly spaced peaks in- creased. These improvements progressed along a low-to- high characteristic frequency gradient. By 10-20 weeks post-treatment, the thresholds and tuning curves of neu- rons with characteristic frequencies below 2000 Hz were within normal limits; however, the spontaneous dis- charge rates of the neurons were still significantly lower than those from normal animals. Key words: Cochlear ganglion neurons - Hair cell regen- eration - Tuning curves - Spontaneous activity - Threshold Abbreviations: KM, kanamycin; BrdU, bromodeoxyuridine; CF, characteristic frequency; CAP, compound action potential; ISI, in- terspike interval Correspondence to: R.J. Salvi Introduction Hair cells and supporting cells in the avian inner ear can regenerate after being destroyed by ototoxic drugs or acoustic overstimulation (Cruz et al. 1987; Corwin and Cotanche 1988; Cotanche 1987a; Ryals and Rubel 1988; Rubel 1992; Hashino et al. 1992a). However, it is not clear whether behavioral and physiological measures of hearing completely recover after the hair cells regenerate or whether the time course of recovery is closely linked to the time course of hair cell regeneration. In the case of acoustic trauma, there are conflicting behavioral and physiological data regarding the degree of recovery. Sev- eral studies have reported that gross potential thresholds and tuning curves in the chick return to normal levels within 10 to 15 days following pure-tone, acoustic over- stimulation (Saunders and Tilney 1982; McFadden and Saunders 1989). By contrast, behavioral thresholds in the budgerigar only partially recovered after exposure to high-level impulse noise resulting in a permanent threshold shift of 20-25 dB at the low frequencies (Hashino et al. 1988). Acoustic trauma preferentially destroys the short hair cells (Cotanche et al. 1987) which are predominantly in- nervated by efferent neurons (von Dfiring et al. 1985) whereas the tall hair cells, which are predominantly in- nervated by afferent neurons, typically survive the trau- ma. Thus, the restoration of hearing following acoustic overstimulation may be due in part to the repair of par- tially damaged hair cells (Cotanche 1987a). Acoustic trauma also damages the upper fibrous layer and lower honeycomb layer of the tectorial membrane, but only the lower honeycomb layer regenerates (Cotanche 1987b; Raphael 1991). Interestingly, the regeneration of the low- er honeycomb layer of the tectorial membrane is corre- lated with the recovery of threshold (McFadden and Saunders 1989). Acoustic trauma also damages the teg- mentum vasculosum, but it recovers at approximately the same rate as the compound action potential (Ryals et al. 1993). Although virtually all of the hair cells regener- ate, the number of cochlear ganglion neurons has been