Modulation Of Excitatory Synaptic Transmission In The Medial Prefrontal Norepinephrine

The prefrontal cortex (PFC) plays a critical role in behaviors requiring a high level of mental integration.Norepinephrine (NE) is a neurotransmitter which is widely distributed throughout the central nervous system. It is known that NE system exerts an important influence on PFC cognitive functions. The adrenoceptors in the PFC comprise a and β-adrenoceptors (ARs). a-adrenoceptors have two subtypes α1-,α2-ARs. Recently, still little is known about the intracellular mechanism that regulates excitatory synaptic transmission via α1-adrenoceptors in the PFC.Stimulation of α1-Adrenoceptors (α1-ARs) in the prefrontal cortex (PFC) affects cognitive function such as working memory, a key function relying on glutamatergic transmission of the PFC network. The present study investigated how α1-AR activation regulates excitatory synaptic transmission in layer Ⅴ-Ⅵ pyramidal cells of the rat medial prefrontal cortex (mPFC). We found that the α1-ARs agonist phenylephrine (Phe) induced a significant enhancement of the amplitude and frequency of non-N-methyl-D-aspartic acid receptors (non-NMDA-Rs) mediated miniature excitatory postsynaptic currents (mEPSCs). The facilitation effect of Phe on the frequency of non-NMDA-Rs mediated mEPSCs was voltage-gated Ca2+ channel dependent. Phe produced a significant enhancement on the amplitude of evoked excitatory postsynaptic currents (eEPSCs), including non-NMDA-Rs and NMDA-Rs mediated eEPSC. Phe decreased the paired-pulse facilitation (PPF) of non-NMDA-Rs mediated eEPSCs and enhanced non-NMDA-Rs mediated inward current evoked by puff application of glutamate. The Phe-induced facilitation of non-NMDA-Rs mediated eEPSCs required G protein, PLC, PKC and ERK. The enhancement of NMDA-Rs mediated eEPSCs by Phe was PKC dependent. This findings suggested that α1-ARs activation facilitatates excitatory synaptic transmission in mPFC pyramidal cells via both pre- and post-synaptic mechanisms.