Serotonin mediates learning-induced potentiation of excitability

J Neurophysiol. 2005 Dec;94(6):4002-10. doi: 10.1152/jn.00432.2005. Epub 2005 Aug 24.

Abstract

Sensitization potentiates excitability in an interneuron, the S-cell, that is critical for this form of learning in the whole-body shortening reflex of the medicinal leech. Serotonin (5-HT) also increases S-cell excitability, and serotonergic modulation is known to be critical for sensitization of whole-body shortening, suggesting that 5-HT mediates learning-induced enhancement of S-cell excitability. In this paper, the role of 5-HT in mediating sensitization-induced potentiation of S-cell excitability was examined. Potentiation of S-cell excitability by 5-HT was blocked by the 5-HT receptor antagonist methysergide and by intracellular injection of the G-protein inhibitor GDP-beta-S, indicating that a metabotropic 5-HT receptor was involved. Bath application of Rp-cAMP, an inhibitor of protein kinase A (PKA), blocked 5-HT-induced potentiation of excitability, whereas db-cAMP, a cAMP analogue that activates PKA, mimicked the potentiating effects of 5-HT on the S-cell. During sensitization of the shortening reflex in semi-intact preparations, methysergide and Rp-cAMP prevented learning-induced potentiation of S-cell excitability, as well as the increase in S-cell activity that normally occurs during sensitization. Furthermore, sensitization-induced increases in the shortening reflex did not occur in preparations treated with methysergide or Rp-cAMP. These results demonstrate that sensitization-induced enhancement of S-cell excitability is mediated by 5-HT and suggests that these changes may contribute to this form of learning.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Analysis of Variance
  • Animals
  • Behavior, Animal
  • Cyclic AMP / analogs & derivatives
  • Cyclic AMP / pharmacology
  • Cyclic CMP / analogs & derivatives
  • Cyclic CMP / pharmacology
  • Drug Interactions
  • Electric Stimulation
  • Enzyme Inhibitors / pharmacology
  • Ganglia, Invertebrate / cytology
  • Ganglia, Invertebrate / drug effects
  • Ganglia, Invertebrate / physiology
  • Guanosine Diphosphate / analogs & derivatives
  • Guanosine Diphosphate / pharmacology
  • Interneurons / drug effects
  • Interneurons / physiology*
  • Learning / drug effects
  • Learning / physiology*
  • Leeches
  • Methysergide / pharmacology
  • Neural Networks, Computer
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Reflex
  • Serotonin / physiology*
  • Serotonin Antagonists / pharmacology
  • Thionucleotides / pharmacology
  • Time Factors

Substances

  • Enzyme Inhibitors
  • Serotonin Antagonists
  • Thionucleotides
  • Guanosine Diphosphate
  • adenosine-3',5'-cyclic phosphorothioate
  • Serotonin
  • Cyclic CMP
  • dibutyryl cyclic-3',5'-cytidine monophosphate
  • guanosine 5'-O-(2-thiodiphosphate)
  • Cyclic AMP
  • Methysergide