Serotonergic modulation of afterhyperpolarization in a neuron that contributes to learning in the leech.
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.
Burrell
Brian D
BD
Neuroscience Group, Division of Basic Biomedical Sciences, Sanford School of Medicine at the University of South Dakota, Vermillion, SD 57069, USA. bburrell@usd.edu
Crisp
Kevin M
KM
D000818:Animals; D001522:Behavior, Animal; D002118:Calcium / Q000378:metabolism; D018999:Charybdotoxin / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D017952:Ganglia, Invertebrate / Q000166:cytology; D007858:Learning / Q000502:physiology*; D007865:Leeches / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D008959:Models, Neurological; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009498:Neurotoxins / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D012530:Saxitoxin / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*; D014403:Tubocurarine / Q000494:pharmacology
D009498:Neurotoxins; D018733:Nicotinic Antagonists; D018999:Charybdotoxin; D012701:Serotonin; D012530:Saxitoxin; D002118:Calcium; D014403:Tubocurarine