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Noradrenergic Suppression of Persistent Firing in Hippocampal CA1 Pyramidal Cells through cAMP-PKA Pathway
Persistent firing is believed to be a cellular correlate of working memory. While the effects of noradrenaline (NA) on working memory have widely been described, its effect on the cellular mechanisms of persistent firing remains largely unknown. Using in vitro intracellular recordings, we demonstrat...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Society for Neuroscience
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009666/ https://www.ncbi.nlm.nih.gov/pubmed/33637539 http://dx.doi.org/10.1523/ENEURO.0440-20.2020 |
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author | Valero-Aracama, Maria Jesus Reboreda, Antonio Arboit, Alberto Sauvage, Magdalena Yoshida, Motoharu |
author_facet | Valero-Aracama, Maria Jesus Reboreda, Antonio Arboit, Alberto Sauvage, Magdalena Yoshida, Motoharu |
author_sort | Valero-Aracama, Maria Jesus |
collection | PubMed |
description | Persistent firing is believed to be a cellular correlate of working memory. While the effects of noradrenaline (NA) on working memory have widely been described, its effect on the cellular mechanisms of persistent firing remains largely unknown. Using in vitro intracellular recordings, we demonstrate that persistent firing is supported by individual neurons in hippocampal CA1 pyramidal cells through cholinergic receptor activation, but is dramatically attenuated by NA. In contrast to the classical theory that recurrent synaptic excitation supports persistent firing, suppression of persistent firing by NA was independent of synaptic transmission, indicating that the mechanism is intrinsic to individual cells. In agreement with detrimental effects of cAMP on working memory, we demonstrate that the suppressive effect of NA was through cAMP-PKA pathway. In addition, activation of β1 and/or β3 adrenergic receptors, which increases cAMP levels, suppressed persistent firing. These results are in line with working memory decline observed during high levels of NA and cAMP, which are implicated in high stress, aging, and schizophrenia. |
format | Online Article Text |
id | pubmed-8009666 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Society for Neuroscience |
record_format | MEDLINE/PubMed |
spelling | pubmed-80096662021-03-31 Noradrenergic Suppression of Persistent Firing in Hippocampal CA1 Pyramidal Cells through cAMP-PKA Pathway Valero-Aracama, Maria Jesus Reboreda, Antonio Arboit, Alberto Sauvage, Magdalena Yoshida, Motoharu eNeuro Research Article: New Research Persistent firing is believed to be a cellular correlate of working memory. While the effects of noradrenaline (NA) on working memory have widely been described, its effect on the cellular mechanisms of persistent firing remains largely unknown. Using in vitro intracellular recordings, we demonstrate that persistent firing is supported by individual neurons in hippocampal CA1 pyramidal cells through cholinergic receptor activation, but is dramatically attenuated by NA. In contrast to the classical theory that recurrent synaptic excitation supports persistent firing, suppression of persistent firing by NA was independent of synaptic transmission, indicating that the mechanism is intrinsic to individual cells. In agreement with detrimental effects of cAMP on working memory, we demonstrate that the suppressive effect of NA was through cAMP-PKA pathway. In addition, activation of β1 and/or β3 adrenergic receptors, which increases cAMP levels, suppressed persistent firing. These results are in line with working memory decline observed during high levels of NA and cAMP, which are implicated in high stress, aging, and schizophrenia. Society for Neuroscience 2021-03-19 /pmc/articles/PMC8009666/ /pubmed/33637539 http://dx.doi.org/10.1523/ENEURO.0440-20.2020 Text en Copyright © 2021 Valero-Aracama et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article: New Research Valero-Aracama, Maria Jesus Reboreda, Antonio Arboit, Alberto Sauvage, Magdalena Yoshida, Motoharu Noradrenergic Suppression of Persistent Firing in Hippocampal CA1 Pyramidal Cells through cAMP-PKA Pathway |
title | Noradrenergic Suppression of Persistent Firing in Hippocampal CA1 Pyramidal Cells through cAMP-PKA Pathway |
title_full | Noradrenergic Suppression of Persistent Firing in Hippocampal CA1 Pyramidal Cells through cAMP-PKA Pathway |
title_fullStr | Noradrenergic Suppression of Persistent Firing in Hippocampal CA1 Pyramidal Cells through cAMP-PKA Pathway |
title_full_unstemmed | Noradrenergic Suppression of Persistent Firing in Hippocampal CA1 Pyramidal Cells through cAMP-PKA Pathway |
title_short | Noradrenergic Suppression of Persistent Firing in Hippocampal CA1 Pyramidal Cells through cAMP-PKA Pathway |
title_sort | noradrenergic suppression of persistent firing in hippocampal ca1 pyramidal cells through camp-pka pathway |
topic | Research Article: New Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009666/ https://www.ncbi.nlm.nih.gov/pubmed/33637539 http://dx.doi.org/10.1523/ENEURO.0440-20.2020 |
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