Characterization of cell types affected by noise-induced tinnitus in the auditory cortex of mice

Detalhes bibliográficos
Autor(a) principal: Sousa, Ingrid Nogueira
Data de Publicação: 2019
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UFRN
Texto Completo: https://repositorio.ufrn.br/jspui/handle/123456789/27679
Resumo: Tinnitus is an abnormal state of nerve cell activity of the auditory system, leading to perception of phantom sounds such as ringing of the ears. Although tinnitus perception is not harmful per se, it can lead to severe psychological stress, anxiety and depression. Several studies indicate the auditory cortex as a potential target for transcranial magnetic/direct current stimulation to alleviate tinnitus perception, yet little is known of how tinnitus alters cortical circuits. Here we investigate cellular populations of layer 5 (L5) of the primary auditory cortex (A1) in a mouse model of noise-induced tinnitus. L5 pyramidal cells (PCs) were routinely subdivided into putative corticofugal projecting type A, or contra-lateral projecting type B PCs, post hoc. We found that membrane properties were different between younger (P16-23) and mature cells (P38-52), and therefore we opted to only include animals ≥1 month of age for noise-overexposure (4-20kHz, 90dB, 1,5 hrs). Next we compared passive and active membrane properties between the two PC subtypes as well between control and tinnitus-like animals. We also used transgenic Chrna2-cre mice to investigate inhibitory Martinotti cells between the experimental groups. We found that noise overexposure did not change passive membrane properties of either type A or type B PCs when examined 5-8 days later. Instead we found type A PCs to fired with a significantly lower firing frequency in response to positive current injections (150pA) following noise overexposure (control A: 20,3±1,8Hz, n=11, noiseoverexposed: 16,1±1,2Hz, n=19, p=0.050), while contrarily type B PCs significantly increased steady state firing frequency (Control B: 13,3±1,3Hz, n=13, noise-overexposed: 19,5±2,4Hz, n=22, p=0,048). Interestingly, preliminary data from Martinotti cells from noise-overexposed animals show a trend of higher initial firing frequency than control (control M: 70,05±6,5Hz, n=8, noise-overexposed: 80,5±3,4Hz, n=12) and steady state frequency (control M: 20,35±4,4Hz, noise-overexposed: 33,5±4,9Hz). Since Martinotti cells are specifically connected to type A PCs through recurrent inhibition, this could suggest that Martinotti cells protects type A PCs from acoustic over-activity. Preliminary data using a genetic activity marker (CaMPARI, n=4 mice) also suggests that noise-overexposure does not affect cells uniformly in layer 5-6 of the A1.Together, these results are a first step in identifying specific cortical neurons affected by noise-induced tinnitus and quantify electrophysiological differences seen for each subtype. To understand the cellular mechanisms of tinnitus is crucial for improving treatments of tinnitus using cortical stimulation.
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spelling Sousa, Ingrid NogueiraLeão, Ricardo Maurício XavierLeão, Richardson NavesLeão, Emelie Katarina Svahn2019-09-06T22:54:38Z2019-09-06T22:54:38Z2019-08-17SOUSA, Ingrid Nogueira. Characterization of cell types affected by noise-induced tinnitus in the auditory cortex of mice. 2019. 51f. Dissertação (Mestrado em Neurociências) - Instituto do Cérebro, Universidade Federal do Rio Grande do Norte, Natal, 2019.https://repositorio.ufrn.br/jspui/handle/123456789/27679Tinnitus is an abnormal state of nerve cell activity of the auditory system, leading to perception of phantom sounds such as ringing of the ears. Although tinnitus perception is not harmful per se, it can lead to severe psychological stress, anxiety and depression. Several studies indicate the auditory cortex as a potential target for transcranial magnetic/direct current stimulation to alleviate tinnitus perception, yet little is known of how tinnitus alters cortical circuits. Here we investigate cellular populations of layer 5 (L5) of the primary auditory cortex (A1) in a mouse model of noise-induced tinnitus. L5 pyramidal cells (PCs) were routinely subdivided into putative corticofugal projecting type A, or contra-lateral projecting type B PCs, post hoc. We found that membrane properties were different between younger (P16-23) and mature cells (P38-52), and therefore we opted to only include animals ≥1 month of age for noise-overexposure (4-20kHz, 90dB, 1,5 hrs). Next we compared passive and active membrane properties between the two PC subtypes as well between control and tinnitus-like animals. We also used transgenic Chrna2-cre mice to investigate inhibitory Martinotti cells between the experimental groups. We found that noise overexposure did not change passive membrane properties of either type A or type B PCs when examined 5-8 days later. Instead we found type A PCs to fired with a significantly lower firing frequency in response to positive current injections (150pA) following noise overexposure (control A: 20,3±1,8Hz, n=11, noiseoverexposed: 16,1±1,2Hz, n=19, p=0.050), while contrarily type B PCs significantly increased steady state firing frequency (Control B: 13,3±1,3Hz, n=13, noise-overexposed: 19,5±2,4Hz, n=22, p=0,048). Interestingly, preliminary data from Martinotti cells from noise-overexposed animals show a trend of higher initial firing frequency than control (control M: 70,05±6,5Hz, n=8, noise-overexposed: 80,5±3,4Hz, n=12) and steady state frequency (control M: 20,35±4,4Hz, noise-overexposed: 33,5±4,9Hz). Since Martinotti cells are specifically connected to type A PCs through recurrent inhibition, this could suggest that Martinotti cells protects type A PCs from acoustic over-activity. Preliminary data using a genetic activity marker (CaMPARI, n=4 mice) also suggests that noise-overexposure does not affect cells uniformly in layer 5-6 of the A1.Together, these results are a first step in identifying specific cortical neurons affected by noise-induced tinnitus and quantify electrophysiological differences seen for each subtype. To understand the cellular mechanisms of tinnitus is crucial for improving treatments of tinnitus using cortical stimulation.O tinnitus é um estado anormal de atividade das células nervosas do sistema auditivo, que leva à percepção de sons fantasmas, como um zumbido nos ouvidos. Embora a percepção do tinnitus não seja prejudicial em si, pode levar a um estresse psicológico grave, a ansiedade e depressão. Vários estudos indicam o córtex auditivo como um alvo potencial para a estimulação transcraniana magnética/corrente contínua para aliviar a percepção do zumbido, mas pouco é conhecido sobre como esse zumbido altera os circuitos corticais. Aqui nós investigamos populações celulares da camada 5 (L5) do córtex auditivo primário (A1) em um modelo de tinnitus induzido por ruído. As células piramidais (PCs) da L5 são rotineiramente subdivididas em tipo A, que projetam corticofugal, ou PC tipo B, com projeção contralateral, post hoc. Encontramos que as propriedades de membrana foram diferentes entre as células mais jovens (P16-23) e as maduras (P38-52) e, portanto, optamos por incluir apenas animais com idade ≥1 mês para a superexposição ao ruído (4-20kHz, 90dB, 1,5 h). Em seguida, comparamos as propriedades ativas e passivas da membrana entre os dois subtipos de PCs, bem como entre animais controle e animais expostos ao ruído. Também usamos camundongos transgênicos Chrna2-cre para investigar a atividade de células inibitórias Martinotti entre os grupos experimentais. Vimos que a superexposição ao ruído não alterou as propriedades passivas da membrana das PCs do tipo A e tipo B quando examinadas de 5 a 8 dias após o trauma. Entretanto, encontramos PCs do tipo A tendo uma frequência de disparo significativamente menor em resposta a injeções de corrente positivas (150pA) após a superexposição ao ruído (controle A: 20,3 ± 1,8Hz, n = 11, ruído superexposto: 16,1 ± 1,2 Hz, n = 19, p = 0,050), enquanto as PCs do tipo B, por outro lado, aumentaram significativamente a frequência de disparo no estado estacionário (Controle B: 13,3 ± 1,3 Hz, n = 13, ruído superexposto: 19,5 ± 2,4 Hz, n = 22, p = 0,048). Interessantemente, dados preliminares das células Martinotti de animais superexpostos ao ruído mostram uma frequência de disparo inicial maior do que o controle (controle M: 70,05 ± 6,5 Hz, n = 8, ruído superexposta: 80,5 ± 3,4 Hz, n = 12), assim como maior frequência de estado estacionário (controle M: 20,35 ± 4,4Hz, ruído superexposto: 33,5 ± 4,9Hz). Como as células Martinotti são especificamente conectadas a PCs tipo A através de inibição recorrente, isso poderia sugerir que as células Martinotti protegem as PCs tipo A contra a hiperatividade acústica. Dados preliminares usando um marcador de atividade genética (CaMPARI, n = 4 ratos) também sugerem que a superexposição ao ruído não afeta as células uniformemente na camada 5-6 do A1. Juntos, esses resultados são um primeiro passo na identificação de neurônios corticais específicos afetados pelo zumbido induzido por ruído e quantificam as diferenças eletrofisiológicas observadas em cada subtipo. Entender os mecanismos celulares do zumbido é crucial para aprimorar os tratamentos utilizando estimulação cortical.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)CNPQ::OUTROS::CIENCIASZumbidoCórtex auditivoPatch ClampCélulas piramidais e células martinottiCharacterization of cell types affected by noise-induced tinnitus in the auditory cortex of miceinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisPROGRAMA DE PÓS-GRADUAÇÃO EM NEUROCIÊNCIASUFRNBrasilinfo:eu-repo/semantics/openAccessporreponame:Repositório Institucional da UFRNinstname:Universidade Federal do Rio Grande do Norte (UFRN)instacron:UFRNORIGINALCharacterizationcelltypes_Sousa_2019.pdfapplication/pdf3667767https://repositorio.ufrn.br/bitstream/123456789/27679/1/Characterizationcelltypes_Sousa_2019.pdf3b917ec04b3cbdf0ec9f212d1919775cMD51TEXTCharacterizationcelltypes_Sousa_2019.pdf.txtCharacterizationcelltypes_Sousa_2019.pdf.txtExtracted texttext/plain98695https://repositorio.ufrn.br/bitstream/123456789/27679/2/Characterizationcelltypes_Sousa_2019.pdf.txt1ba7bc8ddfe5982917f0fac8d79bd43bMD52THUMBNAILCharacterizationcelltypes_Sousa_2019.pdf.jpgCharacterizationcelltypes_Sousa_2019.pdf.jpgGenerated Thumbnailimage/jpeg1164https://repositorio.ufrn.br/bitstream/123456789/27679/3/Characterizationcelltypes_Sousa_2019.pdf.jpg9ad4f5fb278bafe3d05edc8ec72a7e7cMD53123456789/276792019-09-08 02:16:35.885oai:https://repositorio.ufrn.br:123456789/27679Repositório de PublicaçõesPUBhttp://repositorio.ufrn.br/oai/opendoar:2019-09-08T05:16:35Repositório Institucional da UFRN - Universidade Federal do Rio Grande do Norte (UFRN)false
dc.title.pt_BR.fl_str_mv Characterization of cell types affected by noise-induced tinnitus in the auditory cortex of mice
title Characterization of cell types affected by noise-induced tinnitus in the auditory cortex of mice
spellingShingle Characterization of cell types affected by noise-induced tinnitus in the auditory cortex of mice
Sousa, Ingrid Nogueira
CNPQ::OUTROS::CIENCIAS
Zumbido
Córtex auditivo
Patch Clamp
Células piramidais e células martinotti
title_short Characterization of cell types affected by noise-induced tinnitus in the auditory cortex of mice
title_full Characterization of cell types affected by noise-induced tinnitus in the auditory cortex of mice
title_fullStr Characterization of cell types affected by noise-induced tinnitus in the auditory cortex of mice
title_full_unstemmed Characterization of cell types affected by noise-induced tinnitus in the auditory cortex of mice
title_sort Characterization of cell types affected by noise-induced tinnitus in the auditory cortex of mice
author Sousa, Ingrid Nogueira
author_facet Sousa, Ingrid Nogueira
author_role author
dc.contributor.authorID.pt_BR.fl_str_mv
dc.contributor.advisorID.pt_BR.fl_str_mv
dc.contributor.referees1.none.fl_str_mv Leão, Ricardo Maurício Xavier
dc.contributor.referees1ID.pt_BR.fl_str_mv
dc.contributor.referees2.none.fl_str_mv Leão, Richardson Naves
dc.contributor.referees2ID.pt_BR.fl_str_mv
dc.contributor.author.fl_str_mv Sousa, Ingrid Nogueira
dc.contributor.advisor1.fl_str_mv Leão, Emelie Katarina Svahn
contributor_str_mv Leão, Emelie Katarina Svahn
dc.subject.cnpq.fl_str_mv CNPQ::OUTROS::CIENCIAS
topic CNPQ::OUTROS::CIENCIAS
Zumbido
Córtex auditivo
Patch Clamp
Células piramidais e células martinotti
dc.subject.por.fl_str_mv Zumbido
Córtex auditivo
Patch Clamp
Células piramidais e células martinotti
description Tinnitus is an abnormal state of nerve cell activity of the auditory system, leading to perception of phantom sounds such as ringing of the ears. Although tinnitus perception is not harmful per se, it can lead to severe psychological stress, anxiety and depression. Several studies indicate the auditory cortex as a potential target for transcranial magnetic/direct current stimulation to alleviate tinnitus perception, yet little is known of how tinnitus alters cortical circuits. Here we investigate cellular populations of layer 5 (L5) of the primary auditory cortex (A1) in a mouse model of noise-induced tinnitus. L5 pyramidal cells (PCs) were routinely subdivided into putative corticofugal projecting type A, or contra-lateral projecting type B PCs, post hoc. We found that membrane properties were different between younger (P16-23) and mature cells (P38-52), and therefore we opted to only include animals ≥1 month of age for noise-overexposure (4-20kHz, 90dB, 1,5 hrs). Next we compared passive and active membrane properties between the two PC subtypes as well between control and tinnitus-like animals. We also used transgenic Chrna2-cre mice to investigate inhibitory Martinotti cells between the experimental groups. We found that noise overexposure did not change passive membrane properties of either type A or type B PCs when examined 5-8 days later. Instead we found type A PCs to fired with a significantly lower firing frequency in response to positive current injections (150pA) following noise overexposure (control A: 20,3±1,8Hz, n=11, noiseoverexposed: 16,1±1,2Hz, n=19, p=0.050), while contrarily type B PCs significantly increased steady state firing frequency (Control B: 13,3±1,3Hz, n=13, noise-overexposed: 19,5±2,4Hz, n=22, p=0,048). Interestingly, preliminary data from Martinotti cells from noise-overexposed animals show a trend of higher initial firing frequency than control (control M: 70,05±6,5Hz, n=8, noise-overexposed: 80,5±3,4Hz, n=12) and steady state frequency (control M: 20,35±4,4Hz, noise-overexposed: 33,5±4,9Hz). Since Martinotti cells are specifically connected to type A PCs through recurrent inhibition, this could suggest that Martinotti cells protects type A PCs from acoustic over-activity. Preliminary data using a genetic activity marker (CaMPARI, n=4 mice) also suggests that noise-overexposure does not affect cells uniformly in layer 5-6 of the A1.Together, these results are a first step in identifying specific cortical neurons affected by noise-induced tinnitus and quantify electrophysiological differences seen for each subtype. To understand the cellular mechanisms of tinnitus is crucial for improving treatments of tinnitus using cortical stimulation.
publishDate 2019
dc.date.accessioned.fl_str_mv 2019-09-06T22:54:38Z
dc.date.available.fl_str_mv 2019-09-06T22:54:38Z
dc.date.issued.fl_str_mv 2019-08-17
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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dc.identifier.citation.fl_str_mv SOUSA, Ingrid Nogueira. Characterization of cell types affected by noise-induced tinnitus in the auditory cortex of mice. 2019. 51f. Dissertação (Mestrado em Neurociências) - Instituto do Cérebro, Universidade Federal do Rio Grande do Norte, Natal, 2019.
dc.identifier.uri.fl_str_mv https://repositorio.ufrn.br/jspui/handle/123456789/27679
identifier_str_mv SOUSA, Ingrid Nogueira. Characterization of cell types affected by noise-induced tinnitus in the auditory cortex of mice. 2019. 51f. Dissertação (Mestrado em Neurociências) - Instituto do Cérebro, Universidade Federal do Rio Grande do Norte, Natal, 2019.
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