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The Journal of Neuroscience, August 15, 2002, 22(16):6846-6855
Serotonin Receptor Activation Inhibits Sodium Current and Dendritic Excitability in Prefrontal Cortex via a Protein Kinase C-Dependent Mechanism
David B. Carr1, 3, Donald C. Cooper2, 3, Sasha L. Ulrich1, 3, Nelson Spruston2, 3, and D. James Surmeier1, 3 1 Department of Physiology, 2 Department of Neurobiology and Physiology, and 3 Institute for Neuroscience, Northwestern University, Chicago, Illinois 60611
The serotonin (5-HT) innervation of the prefrontal cortex (PFC) exerts a powerful modulatory influence on neuronal activity in this cortical region, although the mechanisms through which 5-HT modulates cellular activity are unclear. Voltage-dependent Na+ channels are one potential target of 5-HT receptor signaling that have wide-ranging effects on activity. Molecular and electrophysiological studies were used to test this potential linkage. Single cell RT-PCR profiling revealed that the vast majority of pyramidal neurons expressed detectable levels of 5-HT2a and/or 5-HT2c receptor mRNA with half of the cells expressing both mRNAs. Whole-cell voltage-clamp recordings of dissociated pyramidal neurons showed that 5-HT2a/c receptor activation reduced rapidly inactivating Na+ currents by reducing maximal current amplitude and shifting fast inactivation voltage dependence. These effects were mediated by Gq activation of phospholipase C, leading to activation of protein kinase C (PKC). 5-HT2a/c receptor stimulation also reduced the amplitude of persistent Na+ current without altering its activation voltage dependence. This modulation was also mediated by PKC. Although 5-HT2a,c receptor activation did not affect somatic action potentials of layer V pyramidal neurons in PFC slices, it did reduce the amplitude of action potentials backpropagating into the apical dendrite. These findings show that 5-HT2a,c receptor activation reduces dendritic excitability and may negatively modulate activity-dependent dendritic synaptic plasticity.
Key words: sodium channel; serotonin; cerebral cortex; scRT-PCR; neuromodulation; voltage-clamp
Copyright © 2002 Society for Neuroscience 0270-6474/02/22166846-10$05.00/0
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