Dopamine transporter is essential for the maintenance of spontaneous activity of auditory nerve neurons and their responsiveness to sound stimulation

Institut National de la Santé et de la Recherche Médicale U583, Institut des Neurosciences de Montpellier and University of Montpellier 1, Montpellier, France.
Journal of Neurochemistry (Impact Factor: 4.28). 05/2006; 97(1):190-200. DOI: 10.1111/j.1471-4159.2006.03722.x
Source: PubMed


Dopamine, a neurotransmitter released by the lateral olivocochlear efferents, has been shown tonically to inhibit the spontaneous and sound-evoked activity of auditory nerve fibres. This permanent inhibition probably requires the presence of an efficient transporter to remove dopamine from the synaptic cleft. Here, we report that the dopamine transporter is located in the lateral efferent fibres both below the inner hair cells and in the inner spiral bundle. Perilymphatic perfusion of the dopamine transporter inhibitors nomifensine and N-[1-(2-benzo[b]thiophenyl)cyclohexyl]piperidine into the cochlea reduced the spontaneous neural noise and the sound-evoked compound action potential of the auditory nerve in a dose-dependent manner, leading to both neural responses being completely abolished. We observed no significant change in cochlear responses generated by sensory hair cells (cochlear microphonic, summating potential, distortion products otoacoustic emissions) or in the endocochlear potential reflecting the functional state of the stria vascularis. This is consistent with a selective action of dopamine transporter inhibitors on auditory nerve activity. Capillary electrophoresis with laser-induced fluorescence (EC-LIF) measurements showed that nomifensine-induced inhibition of auditory nerve responses was due to increased extracellular dopamine levels in the cochlea. Altogether, these results show that the dopamine transporter is essential for maintaining the spontaneous activity of auditory nerve neurones and their responsiveness to sound stimulation.

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Available from: Jérôme Ruel, Mar 17, 2015
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    • "Cochlear perfusion of dopamine reduces sound-evoked neural responses, i.e. cochlear compound action potential (CAP) or single-fiber action potentials, without altering hair-cell generated potentials, such as the cochlear microphonic or the summating potential (Ruel et al., 2001). Similarly, nomifensine-mediated block of the dopamine transporter expressed in LOC terminals in the IHC area (Ruel et al., 2006), reduces the CAP without affecting DPOAEs, presumably by increasing dopamine concentration in the neuropil underneath the IHCs. The inhibitory effects of dopamine are likely mediating the slow-onset neural inhibition that can be observed when activating the LOC system electrically (Groff and Liberman, 2003). "
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