A gain-of-function mutation in the α9 nicotinic acetylcholine receptor alters medial olivocochlear efferent short-term synaptic plasticity

Carolina Wedemeyer, Lucas G. Vattino, Marcelo J. Moglie, Jimena Ballestero, Stéphane F. Maison, Mariano N. Di Guilmi, Julian Taranda, M. Charles Liberman, Paul A. Fuchs, Eleonora Katz, Ana Belén Elgoyhen

Research output: Contribution to journalArticle

Abstract

Gain control of the auditory system operates at multiple levels. Cholinergic medial olivocochlear (MOC) fibers originate in the brainstem and make synaptic contacts at the base of the outer hair cells (OHCs), the final targets of several feedback loops from the periphery and higher-processing centers. Efferent activation inhibitsOHCactive amplification within the mammalian cochlea, through the activation of a calcium-permeable α 9 α 10 ionotropic cholinergic nicotinic receptor (nAChR), functionally coupled to calcium activated SK2 potassium channels. Correct operation of this feedback requires careful matching of acoustic input with the strength of cochlear inhibition (Galambos, 1956; Wiederhold and Kiang, 1970; Gifford and Guinan, 1987), which is driven by the rate of MOCactivity and short-term facilitation at theMOC-OHCsynapse (Ballestero et al., 2011; Katz and Elgoyhen, 2014). The present work shows (in mice of either sex) that a mutation in the α 9α 10 nAChR with increased duration of channel gating (Taranda et al., 2009) greatly elongates hair cell-evoked IPSCs and Ca2+signals. Interestingly, MOC–OHC synapses of L9’T mice presented reduced quantum content and increased presynaptic facilitation. These phenotypic changes lead to enhanced and sustained synaptic responses and OHC hyperpolarization upon high-frequency stimulation of MOC terminals. At the cochlear physiology level these changes were matched by a longer time course of efferent MOC suppression. This indicates that the properties of theMOC-OHCsynapse directly determine the efficacy of the MOCfeedback to the cochlea being a main player in the “gain control” of the auditory periphery.

Original languageEnglish (US)
Pages (from-to)3939-3954
Number of pages16
JournalJournal of Neuroscience
Volume38
Issue number16
DOIs
StatePublished - Apr 2018

Keywords

  • Cochlea
  • Efferent inhibition
  • Hair cells
  • Synaptic plasticity
  • α9α10 nAChR

ASJC Scopus subject areas

  • Neuroscience(all)

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    Wedemeyer, C., Vattino, L. G., Moglie, M. J., Ballestero, J., Maison, S. F., Di Guilmi, M. N., Taranda, J., Liberman, M. C., Fuchs, P. A., Katz, E., & Elgoyhen, A. B. (2018). A gain-of-function mutation in the α9 nicotinic acetylcholine receptor alters medial olivocochlear efferent short-term synaptic plasticity. Journal of Neuroscience, 38(16), 3939-3954. https://doi.org/10.1523/JNEUROSCI.2528-17.2018