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mGluR1 enhances efferent inhibition of inner hair cells in the developing rat cochlea

Ye, Z., Goutman, J. D., Pyott, S. J. & Glowatzki, E., 1-Jun-2017, In : Journal of physiology-London. 595, 11, p. 3483-3495 13 p.

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  • mGluR1 enhances efferent inhibition of inner hair cells in the developing rat cochlea

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Just before the onset of hearing, the inner hair cells (IHCs) receive inhibitory efferent input from cholinergic medial olivocochlear (MOC) neurons originating in the brainstem. This input may serve a role in the maturation of the ascending (afferent) auditory system by inhibiting spontaneous activity of the IHCs. To investigate the molecular mechanisms regulating these IHC efferent synapses, we combined electrical stimulation of the efferent fibres with patch clamp recordings from the IHCs to measure efferent synaptic strength. By examining evoked responses, we show that activation of metabotropic glutamate receptors (mGluRs) by general and group I-specific mGluR agonists enhances IHC efferent inhibition. This enhancement is blocked by application of a group I mGluR1-specific antagonist, indicating that enhancement of IHC efferent inhibition is mediated by group I mGluRs and specifically by mGluR1s. By comparing spontaneous and evoked responses, we show that group I mGluR agonists act presynaptically to increase neurotransmitter release without affecting postsynaptic responsiveness. Moreover, endogenous glutamate released from the IHCs also enhances IHC efferent inhibition via the activation of group I mGluRs. Finally, immunofluorescence analysis indicates that the efferent terminals are sufficiently close to IHC glutamate release sites to allow activation of mGluRs on the efferent terminals by glutamate spillover. Together, these results suggest that glutamate released from the IHCs activates group I mGluRs (mGluR1s), probably present on the efferent terminals, which, in turn, enhances release of acetylcholine and inhibition of the IHCs. Thus, mGluRs establish a local negative feedback loop positioned to regulate IHC activity and maturation of the ascending auditory system in the developing cochlea.

Original languageEnglish
Pages (from-to)3483-3495
Number of pages13
JournalJournal of physiology-London
Volume595
Issue number11
Publication statusPublished - 1-Jun-2017

    Keywords

  • METABOTROPIC GLUTAMATE RECEPTORS, AMINO-ACID RECEPTOR, TRANSMITTER RELEASE, MAMMALIAN COCHLEA, RIBBON SYNAPSE, CALYX SYNAPSE, GROUP-I, MOUSE, MODULATION, EXPRESSION

ID: 47497984