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@ARTICLE{ValeroAracama:155612,
author = {Valero-Aracama, Maria Jesus and Reboreda, Antonio and
Arboit, Alberto and Sauvage, Magdalena and Yoshida,
Motoharu},
title = {{N}oradrenergic {S}uppression of {P}ersistent {F}iring in
{H}ippocampal {CA}1 {P}yramidal {C}ells through c{AMP}-{PKA}
{P}athway.},
journal = {eNeuro},
volume = {8},
number = {2},
issn = {2373-2822},
address = {Washington, DC},
publisher = {Soc.},
reportid = {DZNE-2021-00780},
pages = {ENEURO.0440-20.2020},
year = {2021},
abstract = {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.},
keywords = {Hippocampus / Neurons / Norepinephrine / Pyramidal Cells /
Synaptic Transmission / M1 receptor (Other) / M2/4 receptors
(Other) / PKA (Other) / cAMP (Other) / persistent firing
(Other) / β1 adrenoceptors (Other) / Norepinephrine (NLM
Chemicals)},
cin = {AG Yoshida / AG Angenstein},
ddc = {610},
cid = {I:(DE-2719)1310011 / I:(DE-2719)1310004},
pnm = {351 - Brain Function (POF4-351)},
pid = {G:(DE-HGF)POF4-351},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:33637539},
pmc = {pmc:PMC8009666},
doi = {10.1523/ENEURO.0440-20.2020},
url = {https://pub.dzne.de/record/155612},
}