Norepinephrine drives persistent activity in prefrontal cortex via synergistic α1 and α2 adrenoceptors

Zhang, Zizhen; Cordeiro Matos, Steven; Jego, Sonia; Adamantidis, Antoine Roger; Séguéla, Philippe (2013). Norepinephrine drives persistent activity in prefrontal cortex via synergistic α1 and α2 adrenoceptors. PLoS ONE, 8(6), e66122. Public Library of Science 10.1371/journal.pone.0066122

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Optimal norepinephrine levels in the prefrontal cortex (PFC) increase delay-related firing and enhance working memory, whereas stress-related or pathologically high levels of norepinephrine are believed to inhibit working memory via α1 adrenoceptors. However, it has been shown that activation of Gq-coupled and phospholipase C-linked receptors can induce persistent firing, a cellular correlate of working memory, in cortical pyramidal neurons. Therefore, despite its importance in stress and cognition, the exact role of norepinephrine in modulating PFC activity remains elusive. Using electrophysiology and optogenetics, we report here that norepinephrine induces persistent firing in pyramidal neurons of the PFC independent of recurrent fast synaptic excitation. This persistent excitatory effect involves presynaptic α1 adrenoceptors facilitating glutamate release and subsequent activation of postsynaptic mGluR5 receptors, and is enhanced by postsynaptic α2 adrenoceptors inhibiting HCN channel activity. Activation of α2 adrenoceptors or inhibition of HCN channels also enhances cholinergic persistent responses in pyramidal neurons, providing a mechanism of crosstalk between noradrenergic and cholinergic inputs. The present study describes a novel cellular basis for the noradrenergic control of cortical information processing and supports a synergistic combination of intrinsic and network mechanisms for the expression of mnemonic properties in pyramidal neurons.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology

UniBE Contributor:

Adamantidis, Antoine Roger


600 Technology > 610 Medicine & health




Public Library of Science




Valentina Rossetti

Date Deposited:

18 Jun 2014 16:15

Last Modified:

06 Dec 2014 05:59

Publisher DOI:


PubMed ID:





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