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Stimulation of α2A -adrenoceptors (ARs) in the prefrontal cortex (PFC) produces a beneficial effect on cognitive functions such as working memory. A previous study in our laboratory showed that α2A -AR stimulation suppresses excitatory synaptic transmission in layer V-VI pyramidal cells of the rat medial PFC (mPFC). However, the intracellular mechanism underlying the α2A -AR suppression remains unclear. In the present study, we recorded evoked excitatory postsynaptic current (eEPSC) in layer V-VI pyramidal cells of the mPFC, using whole-cell patch-clamp recording. We found that the α2A -AR agonist guanfacine significantly suppresses eEPSC in mPFC pyramidal cells. The α2A -AR inhibition is mediated by the Gi-cAMP-PKA-PP1-CaMKII-AMPAR signaling pathway, as such inhibition no longer exists when each step of this pathway is blocked with NF023, Rp-cAMP, PKI5-24 or H89, tautomycin, and KN-62 or KN-93, respectively. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Citation

Feng Yi, Shu-Su Liu, Fei Luo, Xue-Han Zhang, Bao-Ming Li. Signaling mechanism underlying α2A -adrenergic suppression of excitatory synaptic transmission in the medial prefrontal cortex of rats. The European journal of neuroscience. 2013 Aug;38(3):2364-73


PMID: 23701442

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