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Cerebral Cortex Advance Access published online on October 26, 2007
Cerebral Cortex, doi:10.1093/cercor/bhm177
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© The Author 2007. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Pre- and Postsynaptic ß-Adrenergic Activation Enhances Excitatory Synaptic Transmission in Layer V/VI Pyramidal Neurons of the Medial Prefrontal Cortex of Rats

Xiao-Hua Ji1, Xiao-Hua Cao1,4, Chun-Lei Zhang1, Ze-Jun Feng1, Xue-Han Zhang1, Lan Ma2,3 and Bao-Ming Li1,2

1 Institute of Neurobiology, Institutes of Brain Science, Fudan University, Shanghai 200032, China, 2 State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Fudan University, Shanghai 200032, China, 3 Pharmacology Research Center, Institutes of Brain Science, Fudan University, Shanghai 200032, China, 4 Shanghai Institute of Brain Functional Genomics, East China Normal University, Shanghai 200062, China

Address correspondence to Bao-Ming Li, PhD, Institute of Neurobiology, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032, China. Email: bmli{at}fudan.edu.cn.

Norepinephrine exerts an important influence on prefrontal cortical functions. The physiological effects of ß-adrenoceptors (ß-ARs) have been examined in other brain regions. However, little is known about ß-AR regulation of synaptic transmission in the prefrontal cortex (PFC). The present study investigated ß-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 ß-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 Ca2+ 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 PKI5–24; 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 ß-AR activation facilitates excitatory synaptic transmission in mPFC pyramidal cells through pre- and postsynaptic mechanisms, probably via cAMP or cAMP/PKA signaling.

Key Words: ß-adrenoceptors • EPSC • isoproterenol • medial prefrontal cortex • rat

The first 2 authors contributed equally to this work


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