title: Serotonin mediates learning-induced potentiation of excitability.
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.
authors.affiliation: Neuroscience Group, Division of Basic Biomedical Sciences, University of South Dakota School of Medicine, Vermillion, 57069, USA. abburrell@usd.edu
authors.forename: Brian D
authors.initials: BD
authors.lastname: Burrell
authors.forename: Christie L
authors.initials: CL
authors.lastname: Sahley
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D003563:Cyclic CMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017952:Ganglia, Invertebrate / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D007858:Learning / Q000187:drug effects / Q000502:physiology*; D007865:Leeches; D008784:Methysergide / Q000494:pharmacology; D016571:Neural Networks, Computer; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D012018:Reflex; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D012702:Serotonin Antagonists; D013873:Thionucleotides; D006153:Guanosine Diphosphate; C016957:adenosine-3',5'-cyclic phosphorothioate; D012701:Serotonin; D003563:Cyclic CMP; C053441:dibutyryl cyclic-3',5'-cytidine monophosphate; C023427:guanosine 5'-O-(2-thiodiphosphate); D000242:Cyclic AMP; D008784:Methysergide