title: Dopamine transporter is essential for the maintenance of spontaneous activity of auditory nerve neurones and their responsiveness to sound stimulation.
abstract: 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U583, Institut des Neurosciences de Montpellier and University of Montpellier 1, Montpellier, France. ruel@montp.inserm.fr
authors.forename: Jérôme
authors.initials: J
authors.lastname: Ruel
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Danielle
authors.initials: D
authors.lastname: Demêmes
authors.forename: Serge
authors.initials: S
authors.lastname: Gobaille
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Puel
authors.forename: Guy
authors.initials: G
authors.lastname: Rebillard
mesh_terms: D000161:Acoustic Stimulation; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D003055:Cochlear Microphonic Potentials / Q000187:drug effects / Q000502:physiology; D003056:Cochlear Nerve / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004525:Efferent Pathways / Q000187:drug effects / Q000502:physiology; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D006199:Hair Cells, Auditory, Inner / Q000187:drug effects / Q000378:metabolism; D006309:Hearing / Q000502:physiology*; D040542:Mechanotransduction, Cellular / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D010498:Perilymph / Q000187:drug effects / Q000378:metabolism; D013136:Spiral Ganglion / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D018492:Dopamine Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; D004298:Dopamine