title: Limited contributions of serotonin to long-term hyperexcitability of Aplysia sensory neurons.
abstract: Serotonin (5-HT) has provided a useful tool to study plasticity of nociceptive sensory neurons in Aplysia. Because noxious stimulation causes release of 5-HT and long-term hyperexcitability (LTH) of sensory neuron somata and because 5-HT treatment can induce long-term synaptic facilitation of sensory neuron synapses, a plausible hypothesis is that 5-HT also induces LTH of the sensory neuron soma. Prolonged or repeated exposure of excised ganglia to 5-HT produced immediate hyperexcitability of sensory neurons that showed little desensitization, but the hyperexcitability decayed within minutes of washing out the 5-HT. Prolonged or repeated treatment of either excised ganglia or dissociated sensory neurons with various concentrations of 5-HT failed to induce significant LTH even when long-term synaptic facilitation was induced in the same preparations. Use of a high-divalent cation solution to reduce interneuron activity during 5-HT treatment failed to enable the induction of LTH in excised ganglia. Pairing 5-HT application with nerve shock failed to enhance LTH produced by nerve shock or to reveal covert LTH produced by 5-HT. The induction of LTH by nerve stimulation was enhanced rather than inhibited by treatment with methiothepin, a 5-HT antagonist reported to block various 5-HT receptors and 5-HT-induced adenylyl cyclase activation. This suggests that endogenous 5-HT may have inhibitory effects on the induction of LTH by noxious stimulation. Methiothepin blocked immediate hyperexcitability produced by exogenous 5-HT and also inhibited the expression of LTH induced by nerve stimulation when applied during testing 1 day afterward. At higher concentrations, methiothepin reduced basal excitability of sensory neurons by mechanisms that may be independent of its antagonism of 5-HT receptors. Several observations suggest that early release of 5-HT and consequent cAMP synthesis in sensory neurons is not important for the induction of LTH by noxious stimulation, whereas later release of 5-HT from persistently activated modulatory neurons, with consequent elevation of cAMP synthesis, may contribute to the maintenance of LTH.
authors.affiliation: Department of Integrative Biology, Pharmacology and Physiology, University of Texas-Houston Medical School, Houston, Texas 77030, USA.
authors.forename: X
authors.initials: X
authors.lastname: Liao
authors.forename: C G
authors.initials: CG
authors.lastname: Brou
authors.forename: E T
authors.initials: ET
authors.lastname: Walters
mesh_terms: D000818:Animals; D001048:Aplysia / Q000502:physiology*; D002478:Cells, Cultured; D004558:Electric Stimulation; D017952:Ganglia, Invertebrate / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008719:Methiothepin / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D012702:Serotonin Antagonists; D012701:Serotonin; D008719:Methiothepin