Activation of serotonin receptors modulates synaptic transmission in rat cerebral cortex

J Neurophysiol. 1999 Dec;82(6):2989-99. doi: 10.1152/jn.1999.82.6.2989.


The cerebral cortex receives an extensive serotonergic (5-hydroxytryptamine, 5-HT) input. Immunohistochemical studies suggest that inhibitory neurons are the main target of 5-HT innervation. In vivo extracellular recordings have shown that 5-HT generally inhibited cortical pyramidal neurons, whereas in vitro studies have shown an excitatory action. To determine the cellular mechanisms underlying the diverse actions of 5-HT in the cortex, we examined its effects on cortical inhibitory interneurons and pyramidal neurons. We found that 5-HT, through activation of 5-HT(2A) receptors, induced a massive enhancement of spontaneous inhibitory postsynaptic currents (sIPSCs) in pyramidal neurons, lasting for approximately 6 min. In interneurons, this 5-HT-induced enhancement of sIPSCs was much weaker. Activation of 5-HT(2A) receptors also increased spontaneous excitatory postsynaptic currents (sEPSCs) in pyramidal neurons. This response desensitized less and at a slower rate. In contrast, 5-HT slightly decreased evoked IPSCs (eIPSCs) and eEPSCs. In addition, 5-HT via 5-HT(3) receptors evoked a large and rapidly desensitizing inward current in a subset of interneurons and induced a transient enhancement of sIPSCs. Our results suggest that 5-HT has widespread effects on both interneurons and pyramidal neurons and that a short pulse of 5-HT is likely to induce inhibition whereas the prolonged presence of 5-HT may result in excitation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cerebral Cortex / cytology
  • Cerebral Cortex / drug effects*
  • Excitatory Postsynaptic Potentials / physiology
  • In Vitro Techniques
  • Interneurons / drug effects
  • Neurons / drug effects
  • Patch-Clamp Techniques
  • Pyramidal Cells / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / physiology*
  • Receptors, Serotonin, 5-HT3
  • Serotonin / pharmacology
  • Serotonin Receptor Agonists / pharmacology*
  • Synaptic Transmission / drug effects*


  • Receptor, Serotonin, 5-HT2A
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT3
  • Serotonin Receptor Agonists
  • Serotonin