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Keywords:

  • α2A-adrenoceptor;
  • excitatory synaptic transmission;
  • intracellular mechanism;
  • medial prefrontal cortex;
  • rat

Abstract

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.