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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...

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Autores principales: Valero-Aracama, Maria Jesus, Reboreda, Antonio, Arboit, Alberto, Sauvage, Magdalena, Yoshida, Motoharu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Society for Neuroscience 2021
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.
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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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