Biphasic modulation of Aplysia siphon motor neurons by the molluscan neuropeptide FMRFamide

The molluscan neuropeptide FMRFamide has an inhibitory effect on the sensory neurons in the neural circuit for the siphon withdrawal reflex. We have explored whether FMRFamide also acts on the postsynaptic LFS motor neurons of this circuit. FMRFamide produces a biphasic response in the majority of LFS-A and LFS-B motor neurons: a fast excitatory response followed by a prolonged inhibitory response. The transient excitatory effect of FMRFamide, which desensitizes rapidly, is due to activation of a Na$\sp+$ current. The late hyperpolarizing phase of the FMRFamide response results from activation of at least two K$\sp+$ currents, one 4-aminopyridine (4-AP) sensitive and one 4-AP insensitive. The late phase of the response also involves an increase in an inward Na$\sp+$ current. Arachidonic acid mimicked the hyperpolarizing phase of the FMRFamide response, and 4-bromophenacyl bromide, an inhibitor of phospholipase A$\sb2$, selectively blocked this component of the FMRFamide response. Although we found several similarities in the cellular mechanisms mediating FMRFamide\u27s presynaptic and postsynaptic actions, the mechanisms are not identical. A subset of LFS neurons exhibit a biphasic, exclusively excitatory response to FMRFamide, consisting of a transient depolarization followed by a prolonged depolarization of reduced magnitude. Over a 29 month period, we consistently observed an increase in the incidence of this exclusively excitatory response between June and September. From October to May, we observed an exclusively excitatory response to FMRFamide in 19% of LFS neurons; in the summer months, 51% of LFS neurons exhibited this type of response. We analyzed the ionic basis of the excitatory/excitatory response to FMRFamide, and observed many similarities to the ionic mechanisms mediating the more frequently observed excitatory/inhibitory response. The exclusively excitatory response involves multiple components: both the transient and prolonged phases of the response involve increases in Na$\sp+$ conductance, and the prolonged phase involves an increase in a 4-AP insensitive outward current as well. The primary difference between the two response types is that FMRFamide fails to activate a 4-AP sensitive K$\sp+$ current in LFS neurons exhibiting an excitatory/excitatory response to the peptide