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

Brian D. Burrell, Kevin M. Crisp

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

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 Ca 2+-free saline, suggesting the involvement of Ca2+- dependent K+ channels. Furthermore, AHP amplitude decreased following treatment with drugs (tubocurare and charybdotoxin) that block Ca 2+-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.

Original languageEnglish (US)
Pages (from-to)605-616
Number of pages12
JournalJournal of Neurophysiology
Volume99
Issue number2
DOIs
StatePublished - Feb 1 2008

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ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

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