Signaling mechanism underlying α2A -adrenergic suppression of excitatory synaptic transmission in the medial prefrontal cortex of rats.
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.
['Yi|Feng|F|', 'Liu|Shu-Su|SS|', 'Luo|Fei|F|', 'Zhang|Xue-Han|XH|', 'Li|Bao-Ming|BM|']
D058647:Adrenergic alpha-2 Receptor Agonists D000818:Animals D019706:Excitatory Postsynaptic Potentials D005260:Female D016316:Guanfacine D066298:In Vitro Techniques D008297:Male D009433:Neural Inhibition D017397:Prefrontal Cortex D017966:Pyramidal Cells D051381:Rats D017207:Rats, Sprague-Dawley D018341:Receptors, Adrenergic, alpha-2 D015398:Signal Transduction
excitatory synaptic transmission medial prefrontal cortex rat intracellular mechanism α2A-adrenoceptor