Serotonin, nitric oxide and histamine enhance the excitability of neuron MCC by diverse mechanisms

Serotonin, nitric oxide (NO) and histamine are neuromodulators used in molluscan nervous systems. We have found that each of them depolarizes and increases the excitability of the serotonergic feeding neural circuit modulator neuron, MCC, of Aplysia, but each induces different changes in background ionic currents and uses a different second messenger. Stimulation of neuron C2 in the cerebral ganglion induces a vsEPSP in MCC using NO and histamine. When these neurons are isolated in culture they form synapses that mediate the vsEPSP. The ionic currents induced by these neuromodulators were investigated in isolated cultured MCCs. Histamine reduced a background outward current between -70 and -30 mV that was blocked by cobalt treatment, indicating that it is a calcium activated potassium current. Serotonin reduced a background outward current from -65 mV to -30 mV and enhanced a potassium inward current more negative than -70 mV that was blocked by cesium and barium. This response was mimicked by 8-Br-cAMP. NO donors reduced a cobalt insensitive background outward current between -70 and -30 mV. This response was mimicked by 8-Br-cGMP. These responses show that MCC can produce complex time and state-dependent activity during its modulation of the feeding neural circuit.