Limited contributions of serotonin to long-term hyperexcitability of Aplysia sensory neurons

Serotonin (5-HT) has provided a useful tool to study plasticity of nocicept ive 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 sensor y 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 o f washing out the 5-HT. Prolonged or repeated treatment of either excised g anglia or dissociated sensory neurons with various concentrations of 5-HT f ailed to induce significant LTH even when longterm synaptic facilitation wa s induced in the same preparations. Use of a high-divalent cation solution to reduce interneuron activity during 5-HT treatment failed to enable the i nduction of LTH in excised ganglia. Pairing 5-HT application with nerve sho ck failed to enhance LTH produced by nerve shock or to reveal covert LTH pr oduced by 5-HT. The induction of LTH by nerve stimulation was enhanced rath er than inhibited by treatment with methiothepin, a 5-HT antagonist reporte d to block various 5-HT receptors and 5-HT-induced adenylyl cyclase activat ion. This suggests that endogenous 5-HT may have inhibitory effects on the induction of LTH by noxious stimulation. Methiothepin blocked immediate hyp erexcitability produced by exogenous 5-HT and also inhibited the expression of LTH induced by nerve stimulation when applied during testing 1 day afte rward. 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 an d consequent cAMP synthesis in sensory neurons is not important for the ind uction of LTH by noxious stimulation, whereas later release of 5-HT from pe rsistently activated modulatory neurons, with consequent elevation of cAMP synthesis, may contribute to the maintenance of LTH.