We have identified a TTX-resistant low-threshold persistent inward sodium current in the cerebral giant cells (CGCs) of Lymnaea, an important state-setting modulatory cell type of molluscan feeding networks. This current has slow voltage-dependent activation and de-activation kinetics, ultra-slow inactivation kinetics and fast de-inactivation kinetics. It activates at approximately -90 mV, peaks at approximately -30 mV, reverses at approximately +35 mV and does not show full voltage-dependent inactivation even at positive voltage steps. Lithium-sodium replacement experiments indicate that the persistent sodium current makes a significant contribution to the CGC membrane potential. Injection of cyclic adenosine monophosphate (cAMP) into the CGC cell body produces a large increase in the persistent sodium current that lasts for several hours. cAMP injection also leads to increased bursting, a significant decrease in the resistance and a significant depolarization of the soma membrane, indicating that cAMP-dependent mechanisms induce prolonged neuronal plasticity in the CGCs. Our observations provide the first link between cAMP-mediated modulation of a TTX-resistant persistent sodium current and prolonged neuronal plasticity in an identified modulatory cell type that plays an important role in behavioral state setting.