Dopamine inhibition of auditory nerve activity in the adult mammalian cochlea

Abstract

Efferent feedback systems provide a means for modulating the input to the central nervous system. The lateral olivocochlear efferents modulate auditory nerve activity via synapses with afferent dendrites below sensory inner hair cells. We examined the effects of dopamine, one of the lateral olivocochlear neurotransmitters, by recording compound and single unit activity from the auditory nerve in adult guinea pigs. Intracochlear application of dopamine reduced the compound action potential (CAP) of the auditory nerve, increased the thresholds and decreased the spontaneous and driven discharge rates of the single unit fibres without changing their frequency-tuning properties. Surprisingly, dopamine antagonists SCH-23390 and eticlopride decreased CAP amplitude as did dopamine. In some units, both SCH-23390 and eticlopride increased the basal activity of auditory nerve fibres leading to an improvement of threshold sensitivity and a decrease of the maximum driven discharge rates to sound. In other units, the increase in firing rate was immediately followed by a marked reduction to values below predrug rates. Because CAP reflects the summed activity of auditory nerve fibres discharging in synchrony, both the decrease in sound-driven discharge rate and the postexcitatory reduction account for the reduction in CAP. Ultrastructural examination of the cochleas perfused with eticlopride showed that some of the afferent dendrites were swollen, suggesting that the marked reduction in firing rate may reflect early signs of excitotoxicity. Results suggest that dopamine may exert a tonic inhibition of the auditory nerve activity. Removal of this tonic inhibition results in the development of early signs of excitotoxicity.

Disruption of Lateral Efferent Pathways: Functional Changes in Auditory Evoked Responses

“…This suggests that DA might ''turn down'' driven activity in the normal auditory system. During infusion of DA agonists, auditory nerve single-unit driven rates (Oestreicher et al 1997;Ruel et al 2001), the whole-nerve response (d'Aldin et al 1995a, b;Ruel et al 2001), and spontaneous firing rates [according to Ruel et al (2001) DA appears to reduce auditory nerve activity, but each of the past de-efferentation investigations (e.g., Liberman 1990;Zheng et al 1999), as well as the current LSO lesion experiment, supports a net excitatory effect of lateral efferent innervation of the cochlea. That is, auditory nerve activity has been depressed in the absence of lateral efferent innervation.…”

“…Although more speculative, we acknowledge there is at least one mechanism through which disruption of DA release by the lateral efferent neurons in the cochlea could result in a depression of CAP amplitude, as shown in the current findings. When DA receptors in the cochlea are blocked with the D1 receptor antagonist eticlopride or the D2 receptor antagonist SCH-23390, high-spontaneous-rate auditory nerve fibers show a transient increase in spontaneous rate followed by a depression in rate (Ruel et al 2001). At least the eticlopride-induced depression in rate is accompanied by auditory nerve dendritic swelling (Ruel et al 2001).…”

“…When DA receptors in the cochlea are blocked with the D1 receptor antagonist eticlopride or the D2 receptor antagonist SCH-23390, high-spontaneous-rate auditory nerve fibers show a transient increase in spontaneous rate followed by a depression in rate (Ruel et al 2001). At least the eticlopride-induced depression in rate is accompanied by auditory nerve dendritic swelling (Ruel et al 2001). If lack of D2 receptor activation underlies dendritic swelling and a related suppression of neural activity, then a lesion that reduces or eliminates the endogenous supply of DA might similarly result in dendritic swelling and depressed auditory nerve activity.…”

Disruption of Lateral Olivocochlear Neurons via a Dopaminergic Neurotoxin Depresses Sound-Evoked Auditory Nerve Activity

“…Dopamine and DA agonists inhibit AN activity (d'Aldin et al 1995a, b;Oestreicher et al 1997;Ruel et al 2001;Sun and Salvi 2001). Both GABA (Felix and Ehrenberger 1992;Malgrange et al 1997;Arnold et al 1998) and enkephalin (Burki et al 1993) similarly inhibit AN activity.…”

Towards a Unifying Basis of Auditory Thresholds: The Effects of Hearing Loss on Temporal Integration Reconsidered

“…The damages that result in reduced sensitivity or gain after noise trauma are more difficult to locate because very peripheral mechanisms, such as those producing conductive hearing loss, as well as presumably central processes such as attention or expectations (Dai and Wright 1995), can affect the sensitivity, possibly also via efferent feedback (e.g., Puel et al 1988;Ruel et al 2001). Nevertheless, damage within the inner ear is most likely to contribute.…”