Serotonin receptor activation inhibits sodium current and dendritic excitability in prefrontal cortex via a protein kinase C-dependent mechanism

David B. Carr, Donald C. Cooper, Sasha L. Ulrich, Nelson Spruston, D. James Surmeier*

*Corresponding author for this work

Research output: Contribution to journalArticle

125 Scopus citations

Abstract

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 back-propagating 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.

Original languageEnglish (US)
Pages (from-to)6846-6855
Number of pages10
JournalJournal of Neuroscience
Volume22
Issue number16
DOIs
StatePublished - Aug 15 2002

Keywords

  • Cerebral cortex
  • Neuromodulation
  • Serotonin
  • Sodium channel
  • Voltage-clamp
  • scRT-PCR

ASJC Scopus subject areas

  • Neuroscience(all)

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