TY  - JOUR
AU  - Valero-Aracama, Maria Jesus
AU  - Reboreda, Antonio
AU  - Arboit, Alberto
AU  - Sauvage, Magdalena
AU  - Yoshida, Motoharu
TI  - Noradrenergic Suppression of Persistent Firing in Hippocampal CA1 Pyramidal Cells through cAMP-PKA Pathway.
JO  - eNeuro
VL  - 8
IS  - 2
SN  - 2373-2822
CY  - Washington, DC
PB  - Soc.
M1  - DZNE-2021-00780
SP  - ENEURO.0440-20.2020
PY  - 2021
AB  - 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.
KW  - Hippocampus
KW  - Neurons
KW  - Norepinephrine
KW  - Pyramidal Cells
KW  - Synaptic Transmission
KW  - M1 receptor (Other)
KW  - M2/4 receptors (Other)
KW  - PKA (Other)
KW  - cAMP (Other)
KW  - persistent firing (Other)
KW  - β1 adrenoceptors (Other)
KW  - Norepinephrine (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:33637539
C2  - pmc:PMC8009666
DO  - DOI:10.1523/ENEURO.0440-20.2020
UR  - https://pub.dzne.de/record/155612
ER  -