A gain-of-function mutation in the α9 nicotinic acetylcholine receptor alters medial olivocochlear efferent short-term synaptic plasticity
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 center...
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2018
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02706474_v38_n16_p3939_Wedemeyer http://hdl.handle.net/20.500.12110/paper_02706474_v38_n16_p3939_Wedemeyer |
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paper:paper_02706474_v38_n16_p3939_Wedemeyer2025-07-30T18:02:51Z A gain-of-function mutation in the α9 nicotinic acetylcholine receptor alters medial olivocochlear efferent short-term synaptic plasticity Cochlea Efferent inhibition Hair cells Synaptic plasticity α9α10 nAChR alpha9 nicotinic acetylcholine receptor nicotinic receptor unclassified drug animal cell animal tissue Article calcium signaling cochlea controlled study efferent nerve enzyme activation facilitation feedback system female gain of function mutation hyperpolarization induced pluripotent stem cell male medial olivocochlear efferent mouse nerve cell plasticity nonhuman outer hair cell phenotype priority journal short term synaptic plasticity 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. © 2018 the authors. 2018 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02706474_v38_n16_p3939_Wedemeyer http://hdl.handle.net/20.500.12110/paper_02706474_v38_n16_p3939_Wedemeyer |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Cochlea Efferent inhibition Hair cells Synaptic plasticity α9α10 nAChR alpha9 nicotinic acetylcholine receptor nicotinic receptor unclassified drug animal cell animal tissue Article calcium signaling cochlea controlled study efferent nerve enzyme activation facilitation feedback system female gain of function mutation hyperpolarization induced pluripotent stem cell male medial olivocochlear efferent mouse nerve cell plasticity nonhuman outer hair cell phenotype priority journal short term synaptic plasticity |
| spellingShingle |
Cochlea Efferent inhibition Hair cells Synaptic plasticity α9α10 nAChR alpha9 nicotinic acetylcholine receptor nicotinic receptor unclassified drug animal cell animal tissue Article calcium signaling cochlea controlled study efferent nerve enzyme activation facilitation feedback system female gain of function mutation hyperpolarization induced pluripotent stem cell male medial olivocochlear efferent mouse nerve cell plasticity nonhuman outer hair cell phenotype priority journal short term synaptic plasticity A gain-of-function mutation in the α9 nicotinic acetylcholine receptor alters medial olivocochlear efferent short-term synaptic plasticity |
| topic_facet |
Cochlea Efferent inhibition Hair cells Synaptic plasticity α9α10 nAChR alpha9 nicotinic acetylcholine receptor nicotinic receptor unclassified drug animal cell animal tissue Article calcium signaling cochlea controlled study efferent nerve enzyme activation facilitation feedback system female gain of function mutation hyperpolarization induced pluripotent stem cell male medial olivocochlear efferent mouse nerve cell plasticity nonhuman outer hair cell phenotype priority journal short term synaptic plasticity |
| description |
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. © 2018 the authors. |
| title |
A gain-of-function mutation in the α9 nicotinic acetylcholine receptor alters medial olivocochlear efferent short-term synaptic plasticity |
| title_short |
A gain-of-function mutation in the α9 nicotinic acetylcholine receptor alters medial olivocochlear efferent short-term synaptic plasticity |
| title_full |
A gain-of-function mutation in the α9 nicotinic acetylcholine receptor alters medial olivocochlear efferent short-term synaptic plasticity |
| title_fullStr |
A gain-of-function mutation in the α9 nicotinic acetylcholine receptor alters medial olivocochlear efferent short-term synaptic plasticity |
| title_full_unstemmed |
A gain-of-function mutation in the α9 nicotinic acetylcholine receptor alters medial olivocochlear efferent short-term synaptic plasticity |
| title_sort |
gain-of-function mutation in the α9 nicotinic acetylcholine receptor alters medial olivocochlear efferent short-term synaptic plasticity |
| publishDate |
2018 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02706474_v38_n16_p3939_Wedemeyer http://hdl.handle.net/20.500.12110/paper_02706474_v38_n16_p3939_Wedemeyer |
| _version_ |
1840320768664141824 |