Serotonergic modulation of afterhyperpolarization in a neuron that contributes to learning in the leech

J Neurophysiol. 2008 Feb;99(2):605-16. doi: 10.1152/jn.00989.2007. Epub 2007 Nov 28.


Modulation of afterhyperpolarization (AHP) represents an important mechanism by which excitability of a neuron can be regulated. In the leech brain, sensitization enhances excitability of the S-cell, an interneuron thought to play an important role in this form of nonassociative learning. This increase in excitability is serotonin (5-HT) dependent, but it is not known whether changes in AHP contribute to 5-HT-mediated enhancement of excitability. Therefore electrophysiological recordings and computational modeling were used to determine whether 5-HT enhances excitability via modulation of AHP. 5-HT reduced S-cell AHP and this decrease in the AHP corresponded with an increase in excitability. Little or no AHP is observed in the presence of Ca2+-free saline, suggesting the involvement of Ca2+-dependent K+ channels. Furthermore, AHP amplitude decreased following treatment with drugs (tubocurare and charybdotoxin) that block Ca2+-dependent K+ channel activity. The S-cell also exhibits an afterdepolarization (ADP), which is usually masked by the AHP, and was inhibited by the Na+ channel blocker saxitoxin. A model of the S-cell AHP was constructed using two Ca2+-dependent K+ currents and a Na+-driven ADP current. Reduction of the model conductances underlying the AHP to mimic the effects of 5-HT was sufficient to enhance excitability. These findings were confirmed in occlusion experiments in which pretreatment with tubocurare was able to block 5-HT-mediated decreases in mAHP levels and increases in excitability. These data show that modulation of S-cell AHP can contribute to 5-HT-mediated increases in excitability and that the S-cell afterpotential is due to the combined effects of AHP- and ADP-producing currents.

Publication types

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

MeSH terms

  • Animals
  • Behavior, Animal
  • Calcium / metabolism
  • Charybdotoxin / pharmacology
  • Dose-Response Relationship, Radiation
  • Drug Interactions
  • Electric Stimulation / methods
  • Ganglia, Invertebrate / cytology
  • Learning / physiology*
  • Leeches / physiology*
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Membrane Potentials / radiation effects
  • Models, Neurological
  • Neurons / classification
  • Neurons / drug effects
  • Neurons / physiology*
  • Neurons / radiation effects
  • Neurotoxins / pharmacology
  • Nicotinic Antagonists / pharmacology
  • Patch-Clamp Techniques / methods
  • Saxitoxin / pharmacology
  • Serotonin / pharmacology
  • Serotonin / physiology*
  • Tubocurarine / pharmacology


  • Neurotoxins
  • Nicotinic Antagonists
  • Charybdotoxin
  • Serotonin
  • Saxitoxin
  • Calcium
  • Tubocurarine