Medial septal dysfunction by ABeta-induced KCNQ channel-block in glutamatergic neurons
Autor(a) principal: | |
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Data de Publicação: | 2011 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRN |
Texto Completo: | https://repositorio.ufrn.br/jspui/handle/123456789/23258 |
Resumo: | Amyloid (A ) peptides play a central role in the pathophysiology of Alzheimer’s disease (AD). The cellular mechanisms underlying A toxicity, however, are poorly understood. Here we show that A 25-35 and A 1-40 acutely and differentially affect the characteristics of 3 classes of medial septum (MS) neurons in mice. In glutamatergic neurons A increases firing frequency and blocks the A- and the M-current (IA and IM, respectively). While the IA block is similar in other MS neuron classes, the block of IM is specific to glutamatergic neurons. IM block and a simulated A block mimic the A -induced increase in spontaneous firing in glutamatergic neurons. Calcium imaging shows that under control conditions glutamatergic neurons rarely fire while nonglutamatergic neurons fire coherently at theta frequencies. A increases the firing rate of glutamatergic neurons while nonglutamatergic neurons lose theta firing coherence. Our results demonstrate that A -induced dysfunction of glutamatergic neurons via IM decrease diminishes MS rhythmicity, which may negatively affect hippocampal rhythmogenesis and underlie the memory loss observed in Alzheimer’s disease. |
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Leão, Richardson NavesLuis V. ColomLotta BorgiusOle KiehnAndré Fisahn2017-05-31T12:11:21Z2017-05-31T12:11:21Z2011-070197-4580https://repositorio.ufrn.br/jspui/handle/123456789/23258engAmyloid Beta peptideMedial septumTheta oscillationsGlutamatergic neuronsCholinergic neuronsGABAergic neuronsM-currentA-currentMedial septal dysfunction by ABeta-induced KCNQ channel-block in glutamatergic neuronsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleAmyloid (A ) peptides play a central role in the pathophysiology of Alzheimer’s disease (AD). The cellular mechanisms underlying A toxicity, however, are poorly understood. Here we show that A 25-35 and A 1-40 acutely and differentially affect the characteristics of 3 classes of medial septum (MS) neurons in mice. In glutamatergic neurons A increases firing frequency and blocks the A- and the M-current (IA and IM, respectively). While the IA block is similar in other MS neuron classes, the block of IM is specific to glutamatergic neurons. IM block and a simulated A block mimic the A -induced increase in spontaneous firing in glutamatergic neurons. Calcium imaging shows that under control conditions glutamatergic neurons rarely fire while nonglutamatergic neurons fire coherently at theta frequencies. A increases the firing rate of glutamatergic neurons while nonglutamatergic neurons lose theta firing coherence. Our results demonstrate that A -induced dysfunction of glutamatergic neurons via IM decrease diminishes MS rhythmicity, which may negatively affect hippocampal rhythmogenesis and underlie the memory loss observed in Alzheimer’s disease.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRNinstname:Universidade Federal do Rio Grande do Norte (UFRN)instacron:UFRNORIGINALMedial septal dysfunction by Aß-induced KCNQ channel-block in glutamatergic neurons.pdfMedial septal dysfunction by Aß-induced KCNQ channel-block in glutamatergic neurons.pdfArtigo completoapplication/pdf1968548https://repositorio.ufrn.br/bitstream/123456789/23258/1/Medial%20septal%20dysfunction%20by%20A%c3%9f-induced%20KCNQ%20channel-block%20in%20glutamatergic%20neurons.pdf6ecdb50c4c2571f6a109b981897b2b8aMD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://repositorio.ufrn.br/bitstream/123456789/23258/2/license.txt8a4605be74aa9ea9d79846c1fba20a33MD52TEXTMedial septal dysfunction by Aß-induced KCNQ channel-block in glutamatergic neurons.pdf.txtMedial septal dysfunction by Aß-induced KCNQ channel-block in glutamatergic neurons.pdf.txtExtracted texttext/plain65091https://repositorio.ufrn.br/bitstream/123456789/23258/5/Medial%20septal%20dysfunction%20by%20A%c3%9f-induced%20KCNQ%20channel-block%20in%20glutamatergic%20neurons.pdf.txt7cfa000442ac81d3fb90ab74f8c6f066MD55THUMBNAILMedial septal dysfunction by Aß-induced KCNQ channel-block in glutamatergic neurons.pdf.jpgMedial septal dysfunction by Aß-induced KCNQ channel-block in glutamatergic neurons.pdf.jpgIM Thumbnailimage/jpeg8652https://repositorio.ufrn.br/bitstream/123456789/23258/6/Medial%20septal%20dysfunction%20by%20A%c3%9f-induced%20KCNQ%20channel-block%20in%20glutamatergic%20neurons.pdf.jpg2aab11c8d26d298b07127a4bd13ac0e3MD56123456789/232582021-07-09 18:25:56.951oai:https://repositorio.ufrn.br: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Repositório de PublicaçõesPUBhttp://repositorio.ufrn.br/oai/opendoar:2021-07-09T21:25:56Repositório Institucional da UFRN - Universidade Federal do Rio Grande do Norte (UFRN)false |
dc.title.pt_BR.fl_str_mv |
Medial septal dysfunction by ABeta-induced KCNQ channel-block in glutamatergic neurons |
title |
Medial septal dysfunction by ABeta-induced KCNQ channel-block in glutamatergic neurons |
spellingShingle |
Medial septal dysfunction by ABeta-induced KCNQ channel-block in glutamatergic neurons Leão, Richardson Naves Amyloid Beta peptide Medial septum Theta oscillations Glutamatergic neurons Cholinergic neurons GABAergic neurons M-current A-current |
title_short |
Medial septal dysfunction by ABeta-induced KCNQ channel-block in glutamatergic neurons |
title_full |
Medial septal dysfunction by ABeta-induced KCNQ channel-block in glutamatergic neurons |
title_fullStr |
Medial septal dysfunction by ABeta-induced KCNQ channel-block in glutamatergic neurons |
title_full_unstemmed |
Medial septal dysfunction by ABeta-induced KCNQ channel-block in glutamatergic neurons |
title_sort |
Medial septal dysfunction by ABeta-induced KCNQ channel-block in glutamatergic neurons |
author |
Leão, Richardson Naves |
author_facet |
Leão, Richardson Naves Luis V. Colom Lotta Borgius Ole Kiehn André Fisahn |
author_role |
author |
author2 |
Luis V. Colom Lotta Borgius Ole Kiehn André Fisahn |
author2_role |
author author author author |
dc.contributor.author.fl_str_mv |
Leão, Richardson Naves Luis V. Colom Lotta Borgius Ole Kiehn André Fisahn |
dc.subject.por.fl_str_mv |
Amyloid Beta peptide Medial septum Theta oscillations Glutamatergic neurons Cholinergic neurons GABAergic neurons M-current A-current |
topic |
Amyloid Beta peptide Medial septum Theta oscillations Glutamatergic neurons Cholinergic neurons GABAergic neurons M-current A-current |
description |
Amyloid (A ) peptides play a central role in the pathophysiology of Alzheimer’s disease (AD). The cellular mechanisms underlying A toxicity, however, are poorly understood. Here we show that A 25-35 and A 1-40 acutely and differentially affect the characteristics of 3 classes of medial septum (MS) neurons in mice. In glutamatergic neurons A increases firing frequency and blocks the A- and the M-current (IA and IM, respectively). While the IA block is similar in other MS neuron classes, the block of IM is specific to glutamatergic neurons. IM block and a simulated A block mimic the A -induced increase in spontaneous firing in glutamatergic neurons. Calcium imaging shows that under control conditions glutamatergic neurons rarely fire while nonglutamatergic neurons fire coherently at theta frequencies. A increases the firing rate of glutamatergic neurons while nonglutamatergic neurons lose theta firing coherence. Our results demonstrate that A -induced dysfunction of glutamatergic neurons via IM decrease diminishes MS rhythmicity, which may negatively affect hippocampal rhythmogenesis and underlie the memory loss observed in Alzheimer’s disease. |
publishDate |
2011 |
dc.date.issued.fl_str_mv |
2011-07 |
dc.date.accessioned.fl_str_mv |
2017-05-31T12:11:21Z |
dc.date.available.fl_str_mv |
2017-05-31T12:11:21Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufrn.br/jspui/handle/123456789/23258 |
dc.identifier.issn.none.fl_str_mv |
0197-4580 |
identifier_str_mv |
0197-4580 |
url |
https://repositorio.ufrn.br/jspui/handle/123456789/23258 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFRN instname:Universidade Federal do Rio Grande do Norte (UFRN) instacron:UFRN |
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Universidade Federal do Rio Grande do Norte (UFRN) |
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UFRN |
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UFRN |
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Repositório Institucional da UFRN |
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Repositório Institucional da UFRN |
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