Trimethyltin disrupts N 1 sensitivity, but has limited effects on the summating potential and cochlear microphonic

Abstract

Trimethyltin (TMT), a model neurotoxicant, has previously been demonstrated to disrupt auditory thresholds in laboratory subjects. In this experiment we characterized the potency of this ototoxicant by means of a dose response study and then evaluated the functional effects of TMT administration when tone-bursts were presented at supra-threshold levels. Guinea pigs were anaesthetized and prepared for electrophysiological measurement of the compound action potential (CAP) and cochlear microphonic (CM). Subsequently averaged wave forms generated by tone-bursts of 0–80 dB SPL were evaluated in order to calculate both a N 1 and a summating potential (SP) input-output function. We show that TMT at doses as low as 0.2 mg/kg produce elevations in N 1, but not in the CM isopotential curve. Using exposures to 0.5 mg/kg TMT we show a profound reduction in the slope of the N 1 input-output curve, but no shift in the SP. The results are consistent with the hypothesis that TMT disrupts function at the synapse between the inner hair cell and the Type1 spiral ganglion cell.