Activation of α1-adrenoceptors enhances excitatory synaptic transmission via a pre- and postsynaptic protein kinase C-dependent mechanism in the medial prefrontal cortex of rats

The physiological effects of α1‐adrenoceptors (α1‐ARs) have been examined in many brain regions. However, little is known about the mechanism of modulation on synaptic transmission by α1‐ARs in the medial prefrontal cortex (mPFC). The present study investigated how α1‐AR activation regulates glutamatergic synaptic transmission in layer V/VI pyramidal cells of the rat mPFC. We found that the α1‐AR agonist phenylephrine (Phe) induced a significant enhancement of the amplitude and frequency of miniature excitatory postsynaptic currents (mEPSCs). The facilitation effect of Phe on the frequency of mEPSCs involved a presynaptic protein kinase C‐dependent pathway. Phe produced a significant enhancement on the amplitude of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor (AMPA‐R)‐ and N‐methyl‐d‐aspartic acid receptor (NMDA‐R)‐mediated evoked excitatory postsynaptic currents (eEPSCs). Phe enhanced inward currents evoked by puff application of glutamate or NMDA. The Phe‐induced facilitation of AMPA‐R‐ and NMDA‐R‐mediated eEPSCs required, in part, postsynaptic Gq, phospholipase C and PKC. These findings suggest that α1‐AR activation facilitates excitatory synaptic transmission in mPFC pyramidal cells via both pre‐ and post‐synaptic PKC‐dependent mechanisms. Little is known about the mechanism of modulation on synaptic transmission by α1‐AR in the medial prefrontal cortex (mPFC). We found that α1‐AR activation enhances glutamatergic transmission in the mPFC by increasing the glutamate release from presynaptic terminals, via PKC‐dependent mechanism, and by enhancing the responsiveness of postsynaptic AMPA‐Rs and NMDA‐Rs, likely via Gq/PLC/PKC signaling pathway.