Serotonin and cAMP induce excitatory modulation of a serotonergic neuron

Serotonin (5-HT) is an excitatory neurotransmitter and neuromodulator. In the Aplysia nervous system it increases excitability and induces spike broadening in sensory neurons. It is released at the synaptic terminals of the metacerebral cells (MCCs) and modulates the feeding neural circuit and buccal muscles during the aroused feeding state. We report that MCC itself is depolarized by 5-HT and becomes excitable. 5-HT induces tonic spike activity and even spike-burst activity. Conceivably, this sensitivity to its own transmitter could provide positive feedback excitation of MCC. Voltage clamp analysis of isolated cultured MCCs shows that 5-HT reduces a calcium-dependent outward current at the resting potential (-60 mV), and enhances steady state inward currents between -55 and -30 mV and between -75 and -100 mV. 8-Br-cAMP has similar effects, suggesting that cAMP mediates the 5-HT effects, in part. A transient calcium current is enhanced at voltages more positive than -40 mV. Barium and cesium selectively block the 5-HT-induced inward current between -75 and -100 mV. Substitution of N-methyl-D-glucamine for sodium and adding cobalt block this current, also indicating that it is a hyperpolarization-activated cation current. The 5-HT-induced inward current between -55 and -30 mV is also blocked by sodium substitution and added cobalt, suggesting that 5-HT increases a depolarization-activated cation current. The outward current that remains when sodium and calcium currents are blocked is reduced by 5-HT. Thus, 5-HT enhances two different cation currents and reduces potassium currents.