Synaptic activity at the MNTB is disrupted in a mouse model with enhanced efferent olivocochlear system

Autores
Di Guilmi, Mariano Nicolás; Boero, Luis Ezequiel; Castagna, Valeria Carolina; Rodríguez Contreras, Adián; Wedemeyer, Carolina; Gomez Casati, Maria Eugenia; Elgoyhen, Ana Belen
Año de publicación
2020
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
The auditory system in many mammals is immature at birth but precisely organized in adults. Spontaneous activity in the inner ear plays a critical role in guiding this process. This is shaped by an efferent pathway that descends from the brainstem and makes transient direct synaptic contacts with inner hair cells (IHCs). In this work, we used an β9 cholinergic receptor knock-in mouse model with enhanced medial efferent activity (Chrna9L9′T, L9′T) to understand the role of the olivocochlear system in the correct establishment of auditory circuits. Wave III amplitudes of auditory brainstem responses (which represent synchronized activity of synapses within the superior olivary complex) were smaller in L9′T mice, suggesting a central dysfunction. The mechanism underlying this functional alteration was analyzed in brain slices containing the medial nucleus of the trapezoid body (MNTB), where neurons are topographically organized along a medio-lateral axis. Electrophysiological recordings evidenced MNTB synaptic alterations. Spontaneous synaptic response (mEPSCs) displayed no changes in its amplitude among genotypes, while mEPSCs mean frequency displayed a significant increase in the L9’T lateral region (M: 2.52±0.56 Hz; L: 345 7.17±1.94 Hz; Mann-Whitney test, Z: -2.11, p=0.035). Moreover, evoked synaptic transmission was altered in the transgenic mice. While no significant differences in the unitary medial and lateral EPSC amplitudes were recorded in WT mice (M: 7.59±1.12 nA, n=9, 7 animals; L: 7.35±0.95 nA, n=10, 8 animals, ANOVA, F:0.027, p=0.87), evoked synaptic currents in the lateral side (5.07±0.87 nA, n=12, 11 animals) of L9’T mice were smaller compared to those of the medial side (8.05±1.37 nA, n=11, 11 animals; ANOVA, F:5.07, p=0.0357). These abnormalities were further supported by morphological alterations. Rhodamine-dextran labeling evidenced multiple innervation in L9’T MNTB principal cells suggesting an impairment during development. At the in-vivo level, multielectrode recordings showed that the overall level of MNTB activity was reduced in the L9’T. The average multi-unit activity in WT (11.49±3.58 Hz, n=6 animals) was larger than in L9’T mice (2.53-±0.43 Hz, n=8 animals; Mann-Whitney U Test, Z=2.19, 806 p=0.028). The present results suggest that the transient cochlear efferent innervation to IHCs during the critical period before the onset of hearing is involved in the refinement of topographic maps as well as in setting the correct synaptic transmission at central auditory nuclei.
Fil: Di Guilmi, Mariano Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Boero, Luis Ezequiel. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Castagna, Valeria Carolina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Rodríguez Contreras, Adián. City University Of New York. The City College Of New York.; Estados Unidos
Fil: Wedemeyer, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Gomez Casati, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacologia; Argentina
Fil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
ARO 43rd Annual MidWinter Meeting
California
Estados Unidos
Association for Research in Otolaryngology
Materia
MNTB
OLIVOCOCHLEAR
TONOTOPY
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/203242
Acceder
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Synaptic activity at the MNTB is disrupted in a mouse model with enhanced efferent olivocochlear systemDi Guilmi, Mariano NicolásBoero, Luis EzequielCastagna, Valeria CarolinaRodríguez Contreras, AdiánWedemeyer, CarolinaGomez Casati, Maria EugeniaElgoyhen, Ana BelenMNTBOLIVOCOCHLEARTONOTOPYhttps://purl.org/becyt/ford/1.7https://purl.org/becyt/ford/1The auditory system in many mammals is immature at birth but precisely organized in adults. Spontaneous activity in the inner ear plays a critical role in guiding this process. This is shaped by an efferent pathway that descends from the brainstem and makes transient direct synaptic contacts with inner hair cells (IHCs). In this work, we used an β9 cholinergic receptor knock-in mouse model with enhanced medial efferent activity (Chrna9L9′T, L9′T) to understand the role of the olivocochlear system in the correct establishment of auditory circuits. Wave III amplitudes of auditory brainstem responses (which represent synchronized activity of synapses within the superior olivary complex) were smaller in L9′T mice, suggesting a central dysfunction. The mechanism underlying this functional alteration was analyzed in brain slices containing the medial nucleus of the trapezoid body (MNTB), where neurons are topographically organized along a medio-lateral axis. Electrophysiological recordings evidenced MNTB synaptic alterations. Spontaneous synaptic response (mEPSCs) displayed no changes in its amplitude among genotypes, while mEPSCs mean frequency displayed a significant increase in the L9’T lateral region (M: 2.52±0.56 Hz; L: 345 7.17±1.94 Hz; Mann-Whitney test, Z: -2.11, p=0.035). Moreover, evoked synaptic transmission was altered in the transgenic mice. While no significant differences in the unitary medial and lateral EPSC amplitudes were recorded in WT mice (M: 7.59±1.12 nA, n=9, 7 animals; L: 7.35±0.95 nA, n=10, 8 animals, ANOVA, F:0.027, p=0.87), evoked synaptic currents in the lateral side (5.07±0.87 nA, n=12, 11 animals) of L9’T mice were smaller compared to those of the medial side (8.05±1.37 nA, n=11, 11 animals; ANOVA, F:5.07, p=0.0357). These abnormalities were further supported by morphological alterations. Rhodamine-dextran labeling evidenced multiple innervation in L9’T MNTB principal cells suggesting an impairment during development. At the in-vivo level, multielectrode recordings showed that the overall level of MNTB activity was reduced in the L9’T. The average multi-unit activity in WT (11.49±3.58 Hz, n=6 animals) was larger than in L9’T mice (2.53-±0.43 Hz, n=8 animals; Mann-Whitney U Test, Z=2.19, 806 p=0.028). The present results suggest that the transient cochlear efferent innervation to IHCs during the critical period before the onset of hearing is involved in the refinement of topographic maps as well as in setting the correct synaptic transmission at central auditory nuclei.Fil: Di Guilmi, Mariano Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Boero, Luis Ezequiel. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Castagna, Valeria Carolina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Rodríguez Contreras, Adián. City University Of New York. The City College Of New York.; Estados UnidosFil: Wedemeyer, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Gomez Casati, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacologia; ArgentinaFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaARO 43rd Annual MidWinter MeetingCaliforniaEstados UnidosAssociation for Research in OtolaryngologyAssociation for Research in Otolaryngology2020info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/203242Synaptic activity at the MNTB is disrupted in a mouse model with enhanced efferent olivocochlear system; ARO 43rd Annual MidWinter Meeting; California; Estados Unidos; 2020; 534-535CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://aro.org/wp-content/uploads/2020/02/2020-Abstracts_1-21-20-Web.pdfInternacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:51:31Zoai:ri.conicet.gov.ar:11336/203242instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:51:31.753CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Synaptic activity at the MNTB is disrupted in a mouse model with enhanced efferent olivocochlear system
title Synaptic activity at the MNTB is disrupted in a mouse model with enhanced efferent olivocochlear system
spellingShingle Synaptic activity at the MNTB is disrupted in a mouse model with enhanced efferent olivocochlear system
Di Guilmi, Mariano Nicolás
MNTB
OLIVOCOCHLEAR
TONOTOPY
title_short Synaptic activity at the MNTB is disrupted in a mouse model with enhanced efferent olivocochlear system
title_full Synaptic activity at the MNTB is disrupted in a mouse model with enhanced efferent olivocochlear system
title_fullStr Synaptic activity at the MNTB is disrupted in a mouse model with enhanced efferent olivocochlear system
title_full_unstemmed Synaptic activity at the MNTB is disrupted in a mouse model with enhanced efferent olivocochlear system
title_sort Synaptic activity at the MNTB is disrupted in a mouse model with enhanced efferent olivocochlear system
dc.creator.none.fl_str_mv Di Guilmi, Mariano Nicolás
Boero, Luis Ezequiel
Castagna, Valeria Carolina
Rodríguez Contreras, Adián
Wedemeyer, Carolina
Gomez Casati, Maria Eugenia
Elgoyhen, Ana Belen
author Di Guilmi, Mariano Nicolás
author_facet Di Guilmi, Mariano Nicolás
Boero, Luis Ezequiel
Castagna, Valeria Carolina
Rodríguez Contreras, Adián
Wedemeyer, Carolina
Gomez Casati, Maria Eugenia
Elgoyhen, Ana Belen
author_role author
author2 Boero, Luis Ezequiel
Castagna, Valeria Carolina
Rodríguez Contreras, Adián
Wedemeyer, Carolina
Gomez Casati, Maria Eugenia
Elgoyhen, Ana Belen
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv MNTB
OLIVOCOCHLEAR
TONOTOPY
topic MNTB
OLIVOCOCHLEAR
TONOTOPY
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.7
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The auditory system in many mammals is immature at birth but precisely organized in adults. Spontaneous activity in the inner ear plays a critical role in guiding this process. This is shaped by an efferent pathway that descends from the brainstem and makes transient direct synaptic contacts with inner hair cells (IHCs). In this work, we used an β9 cholinergic receptor knock-in mouse model with enhanced medial efferent activity (Chrna9L9′T, L9′T) to understand the role of the olivocochlear system in the correct establishment of auditory circuits. Wave III amplitudes of auditory brainstem responses (which represent synchronized activity of synapses within the superior olivary complex) were smaller in L9′T mice, suggesting a central dysfunction. The mechanism underlying this functional alteration was analyzed in brain slices containing the medial nucleus of the trapezoid body (MNTB), where neurons are topographically organized along a medio-lateral axis. Electrophysiological recordings evidenced MNTB synaptic alterations. Spontaneous synaptic response (mEPSCs) displayed no changes in its amplitude among genotypes, while mEPSCs mean frequency displayed a significant increase in the L9’T lateral region (M: 2.52±0.56 Hz; L: 345 7.17±1.94 Hz; Mann-Whitney test, Z: -2.11, p=0.035). Moreover, evoked synaptic transmission was altered in the transgenic mice. While no significant differences in the unitary medial and lateral EPSC amplitudes were recorded in WT mice (M: 7.59±1.12 nA, n=9, 7 animals; L: 7.35±0.95 nA, n=10, 8 animals, ANOVA, F:0.027, p=0.87), evoked synaptic currents in the lateral side (5.07±0.87 nA, n=12, 11 animals) of L9’T mice were smaller compared to those of the medial side (8.05±1.37 nA, n=11, 11 animals; ANOVA, F:5.07, p=0.0357). These abnormalities were further supported by morphological alterations. Rhodamine-dextran labeling evidenced multiple innervation in L9’T MNTB principal cells suggesting an impairment during development. At the in-vivo level, multielectrode recordings showed that the overall level of MNTB activity was reduced in the L9’T. The average multi-unit activity in WT (11.49±3.58 Hz, n=6 animals) was larger than in L9’T mice (2.53-±0.43 Hz, n=8 animals; Mann-Whitney U Test, Z=2.19, 806 p=0.028). The present results suggest that the transient cochlear efferent innervation to IHCs during the critical period before the onset of hearing is involved in the refinement of topographic maps as well as in setting the correct synaptic transmission at central auditory nuclei.
Fil: Di Guilmi, Mariano Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Boero, Luis Ezequiel. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Castagna, Valeria Carolina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Rodríguez Contreras, Adián. City University Of New York. The City College Of New York.; Estados Unidos
Fil: Wedemeyer, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Gomez Casati, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacologia; Argentina
Fil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
ARO 43rd Annual MidWinter Meeting
California
Estados Unidos
Association for Research in Otolaryngology
description The auditory system in many mammals is immature at birth but precisely organized in adults. Spontaneous activity in the inner ear plays a critical role in guiding this process. This is shaped by an efferent pathway that descends from the brainstem and makes transient direct synaptic contacts with inner hair cells (IHCs). In this work, we used an β9 cholinergic receptor knock-in mouse model with enhanced medial efferent activity (Chrna9L9′T, L9′T) to understand the role of the olivocochlear system in the correct establishment of auditory circuits. Wave III amplitudes of auditory brainstem responses (which represent synchronized activity of synapses within the superior olivary complex) were smaller in L9′T mice, suggesting a central dysfunction. The mechanism underlying this functional alteration was analyzed in brain slices containing the medial nucleus of the trapezoid body (MNTB), where neurons are topographically organized along a medio-lateral axis. Electrophysiological recordings evidenced MNTB synaptic alterations. Spontaneous synaptic response (mEPSCs) displayed no changes in its amplitude among genotypes, while mEPSCs mean frequency displayed a significant increase in the L9’T lateral region (M: 2.52±0.56 Hz; L: 345 7.17±1.94 Hz; Mann-Whitney test, Z: -2.11, p=0.035). Moreover, evoked synaptic transmission was altered in the transgenic mice. While no significant differences in the unitary medial and lateral EPSC amplitudes were recorded in WT mice (M: 7.59±1.12 nA, n=9, 7 animals; L: 7.35±0.95 nA, n=10, 8 animals, ANOVA, F:0.027, p=0.87), evoked synaptic currents in the lateral side (5.07±0.87 nA, n=12, 11 animals) of L9’T mice were smaller compared to those of the medial side (8.05±1.37 nA, n=11, 11 animals; ANOVA, F:5.07, p=0.0357). These abnormalities were further supported by morphological alterations. Rhodamine-dextran labeling evidenced multiple innervation in L9’T MNTB principal cells suggesting an impairment during development. At the in-vivo level, multielectrode recordings showed that the overall level of MNTB activity was reduced in the L9’T. The average multi-unit activity in WT (11.49±3.58 Hz, n=6 animals) was larger than in L9’T mice (2.53-±0.43 Hz, n=8 animals; Mann-Whitney U Test, Z=2.19, 806 p=0.028). The present results suggest that the transient cochlear efferent innervation to IHCs during the critical period before the onset of hearing is involved in the refinement of topographic maps as well as in setting the correct synaptic transmission at central auditory nuclei.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Reunión
Book
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/203242
Synaptic activity at the MNTB is disrupted in a mouse model with enhanced efferent olivocochlear system; ARO 43rd Annual MidWinter Meeting; California; Estados Unidos; 2020; 534-535
CONICET Digital
CONICET
url http://hdl.handle.net/11336/203242
identifier_str_mv Synaptic activity at the MNTB is disrupted in a mouse model with enhanced efferent olivocochlear system; ARO 43rd Annual MidWinter Meeting; California; Estados Unidos; 2020; 534-535
CONICET Digital
CONICET
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language eng
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application/pdf
application/pdf
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dc.coverage.none.fl_str_mv Internacional
dc.publisher.none.fl_str_mv Association for Research in Otolaryngology
publisher.none.fl_str_mv Association for Research in Otolaryngology
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repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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