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Norepinephrine exerts an important influence on prefrontal cortical functions. The physiological effects of beta-adrenoceptors (beta-ARs) have been examined in other brain regions. However, little is known about beta-AR regulation of synaptic transmission in the prefrontal cortex (PFC). The present study investigated beta-AR modulation of glutamate synaptic transmission in layer V/VI pyramidal cells of the medial PFC (mPFC) of rats. Our results show that 1) isoproterenol (ISO), a selective beta-AR agonist, increased the frequency of spontaneous and miniature excitatory postsynaptic currents (EPSC's); 2) ISO enhancement of miniature EPSC's (mEPSC's) frequency no longer appeared in the presence of the voltage-gated Ca(2+) channel blocker cadmium; 3) ISO enhanced the evoked excitatory postsynaptic currents (eEPSC's) mediated by non-N-methyl-D-aspartic acid receptors (non-NMDA-Rs) and NMDA-Rs. The ISO facilitation of non-NMDA-R eEPSC was blocked by the membrane-permeable cyclic adenosine monophosphate (cAMP) inhibitor Rp-adenosine 3',5'-cyclic monophosphorothioate triethylammonium salt (Rp-cAMPS); 4) ISO enhanced NMDA-induced current, with no effect on glutamate-induced non-NMDA-R current; 5) ISO enhancement of NMDA-R eEPSC and NMDA-induced current was blocked by intracellular application of Rp-cAMPS or the cAMP-dependent protein kinase (PKA) inhibitor PKI(5-24); and 6) ISO suppressed the paired-pulse facilitation of non-NMDA-R and NMDA-R eEPSC's. Taken together, these results provide the first electrophysiological demonstration that beta-AR activation facilitates excitatory synaptic transmission in mPFC pyramidal cells through pre- and postsynaptic mechanisms, probably via cAMP or cAMP/PKA signaling.

Citation

Xiao-Hua Ji, Xiao-Hua Cao, Chun-Lei Zhang, Ze-Jun Feng, Xue-Han Zhang, Lan Ma, Bao-Ming Li. Pre- and postsynaptic beta-adrenergic activation enhances excitatory synaptic transmission in layer V/VI pyramidal neurons of the medial prefrontal cortex of rats. Cerebral cortex (New York, N.Y. : 1991). 2008 Jul;18(7):1506-20

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PMID: 17965126

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