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...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: 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.
Formato: JOUR
Materias:
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_02706474_v38_n16_p3939_Wedemeyer
Aporte de:
id todo:paper_02706474_v38_n16_p3939_Wedemeyer
record_format dspace
spelling todo:paper_02706474_v38_n16_p3939_Wedemeyer2023-10-03T15:14:48Z A gain-of-function mutation in the α9 nicotinic acetylcholine receptor alters medial olivocochlear efferent short-term synaptic plasticity 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. 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar 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
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.
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.
format JOUR
author 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.
author_facet 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.
author_sort Wedemeyer, C.
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
url http://hdl.handle.net/20.500.12110/paper_02706474_v38_n16_p3939_Wedemeyer
work_keys_str_mv AT wedemeyerc againoffunctionmutationinthea9nicotinicacetylcholinereceptoraltersmedialolivocochlearefferentshorttermsynapticplasticity
AT vattinolg againoffunctionmutationinthea9nicotinicacetylcholinereceptoraltersmedialolivocochlearefferentshorttermsynapticplasticity
AT mogliemj againoffunctionmutationinthea9nicotinicacetylcholinereceptoraltersmedialolivocochlearefferentshorttermsynapticplasticity
AT ballesteroj againoffunctionmutationinthea9nicotinicacetylcholinereceptoraltersmedialolivocochlearefferentshorttermsynapticplasticity
AT maisonsf againoffunctionmutationinthea9nicotinicacetylcholinereceptoraltersmedialolivocochlearefferentshorttermsynapticplasticity
AT diguilmimn againoffunctionmutationinthea9nicotinicacetylcholinereceptoraltersmedialolivocochlearefferentshorttermsynapticplasticity
AT tarandaj againoffunctionmutationinthea9nicotinicacetylcholinereceptoraltersmedialolivocochlearefferentshorttermsynapticplasticity
AT libermanmc againoffunctionmutationinthea9nicotinicacetylcholinereceptoraltersmedialolivocochlearefferentshorttermsynapticplasticity
AT fuchspa againoffunctionmutationinthea9nicotinicacetylcholinereceptoraltersmedialolivocochlearefferentshorttermsynapticplasticity
AT katze againoffunctionmutationinthea9nicotinicacetylcholinereceptoraltersmedialolivocochlearefferentshorttermsynapticplasticity
AT elgoyhenab againoffunctionmutationinthea9nicotinicacetylcholinereceptoraltersmedialolivocochlearefferentshorttermsynapticplasticity
AT wedemeyerc gainoffunctionmutationinthea9nicotinicacetylcholinereceptoraltersmedialolivocochlearefferentshorttermsynapticplasticity
AT vattinolg gainoffunctionmutationinthea9nicotinicacetylcholinereceptoraltersmedialolivocochlearefferentshorttermsynapticplasticity
AT mogliemj gainoffunctionmutationinthea9nicotinicacetylcholinereceptoraltersmedialolivocochlearefferentshorttermsynapticplasticity
AT ballesteroj gainoffunctionmutationinthea9nicotinicacetylcholinereceptoraltersmedialolivocochlearefferentshorttermsynapticplasticity
AT maisonsf gainoffunctionmutationinthea9nicotinicacetylcholinereceptoraltersmedialolivocochlearefferentshorttermsynapticplasticity
AT diguilmimn gainoffunctionmutationinthea9nicotinicacetylcholinereceptoraltersmedialolivocochlearefferentshorttermsynapticplasticity
AT tarandaj gainoffunctionmutationinthea9nicotinicacetylcholinereceptoraltersmedialolivocochlearefferentshorttermsynapticplasticity
AT libermanmc gainoffunctionmutationinthea9nicotinicacetylcholinereceptoraltersmedialolivocochlearefferentshorttermsynapticplasticity
AT fuchspa gainoffunctionmutationinthea9nicotinicacetylcholinereceptoraltersmedialolivocochlearefferentshorttermsynapticplasticity
AT katze gainoffunctionmutationinthea9nicotinicacetylcholinereceptoraltersmedialolivocochlearefferentshorttermsynapticplasticity
AT elgoyhenab gainoffunctionmutationinthea9nicotinicacetylcholinereceptoraltersmedialolivocochlearefferentshorttermsynapticplasticity
_version_ 1807323472039247872