Institute of Neurobiology & State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Fudan University, Shanghai 200032, China.
Eur J Neurosci. 2013 Aug;38(3):2364-73. doi: 10.1111/ejn.12257. Epub 2013 May 23.
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.
α2A-肾上腺素受体（ARs）在前额叶皮层（PFC）的刺激对工作记忆等认知功能产生有益的影响。我们实验室的先前研究表明，α2A-AR 刺激抑制大鼠内侧前额叶皮层（mPFC）的 V-VI 层锥体神经元中的兴奋性突触传递。然而，α2A-AR 抑制的细胞内机制仍不清楚。在本研究中，我们使用全细胞膜片钳记录在 mPFC 的 V-VI 层锥体神经元中记录诱发的兴奋性突触后电流（eEPSC）。我们发现，α2A-AR 激动剂胍法辛可显著抑制 mPFC 锥体神经元中的 eEPSC。α2A-AR 抑制是由 Gi-cAMP-PKA-PP1-CaMKII-AMPA 信号通路介导的，因为当该通路的每一步分别用 NF023、Rp-cAMP、PKI5-24 或 H89、 tautomycin 和 KN-62 或 KN-93 阻断时，这种抑制就不再存在。
