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.