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

WEDEMEYER, CAROLINA; MOGLIE, MARCELO J.; BALLESTERO, JIMENA; DI GUILMI, MARIANO N.; TARANDA, JULIAN; FUCHS, PAUL A.; KATZ, ELEONORA; VATTINO, LUCAS G.; VATTINO, LUCAS G.; WEDEMEYER, CAROLINA; BALLESTERO, JIMENA; MAISON, STÉPHANE F.; MAISON, STÉPHANE F.; LIBERMAN, M. CHARLES; TARANDA, JULIAN; LIBERMAN, M. CHARLES; ELGOYHEN, ANA BELÉN; KATZ, ELEONORA; ELGOYHEN, ANA BELÉN; MOGLIE, MARCELO J.; DI GUILMI, MARIANO N.; FUCHS, PAUL A.

JOURNAL OF NEUROSCIENCE

SOC NEUROSCIENCE

Año: 2018 vol. 38 p. 3939 - 3954

0270-6474

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.