Journal Article

DZNE-2021-00780

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Noradrenergic Suppression of Persistent Firing in Hippocampal CA1 Pyramidal Cells through cAMP-PKA Pathway.

Valero-Aracama, M. J. ; Reboreda, A.DZNE* ; Arboit, A.DZNE* ; Sauvage, M. ; Yoshida, M. (Last author)DZNE*

2021
Soc. Washington, DC

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Please use a persistent id in citations: doi:10.1523/ENEURO.0440-20.2020

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.

Keyword(s): Hippocampus (MeSH) ; Neurons (MeSH) ; Norepinephrine (MeSH) ; Pyramidal Cells (MeSH) ; Synaptic Transmission (MeSH) ; M1 receptor ; M2/4 receptors ; PKA ; cAMP ; persistent firing ; β1 adrenoceptors ; Norepinephrine

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Contributing Institute(s):

1. Cognitive Neurophysiology (AG Yoshida)
2. Functional Neuroimaging (AG Angenstein)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)

Appears in the scientific report 2021

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