Dopamine inhibition of auditory nerve activity in the adult mammalian cochlea

Efferent feedback systems provide a means for modulating the input to the c entral nervous system. The lateral olivocochlear efferents modulate auditor y nerve activity via synapses with afferent dendrites below sensory inner h air cells. We examined the effects of dopamine, one of the lateral olivococ hlear neurotransmitters, by recording compound and single unit activity fro m the auditory nerve in adult guinea pigs. Intracochlear application of dop amine reduced the compound action potential (CAP) of the auditory nerve, in creased the thresholds and decreased the spontaneous and driven discharge r ates of the single unit fibres without changing their frequency-tuning prop erties. Surprisingly, dopamine antagonists SCH-23390 and eticlopride decrea sed CAP amplitude as did dopamine. In some units, both SCH-23390 and eticlo pride increased the basal activity of auditory nerve fibres leading to an i mprovement of threshold sensitivity and a decrease of the maximum driven di scharge rates to sound. In other units, the increase in firing rate was imm ediately followed by a marked reduction to values below predrug rates. Beca use CAP reflects the summed activity of auditory nerve fibres discharging i n synchrony, both the decrease in sound-driven discharge rate and the poste xcitatory reduction account for the reduction in CAP. Ultrastructural exami nation of the cochleas perfused with eticlopride showed that some of the af ferent dendrites were swollen, suggesting that the marked reduction in firi ng rate may reflect early signs of excitotoxicity. Results suggest that dop amine may exert a tonic inhibition of the auditory nerve activity. Removal of this tonic inhibition results in the development of early signs of excit otoxcity.