Abstract | Facilitation of sensory neuron synapses in Aplysia californica is induced by the neurotransmitter serotonin (5-HT). This strengthening of synaptic transmission can be mediated by the activation of protein kinase C (PKC), which regulates transmitter release, ion channel function, cytoskeletal rearrangement and gene expression. PKC activation is sensitive to the method of 5-HT application. Spaced application of 5-HT (five 5-min applications of 5-HT with an inter application interval of 15-min) strongly desensitizes PKC activation, while prolonged application of 5-HT leads only to weak desensitization of PKC. Inhibition of protein kinase A (PKA) results in a decrease of PKC desensitization for both spaced and massed application of 5-HT. In contrast, applying a protein translation inhibitor drastically increases the desensitization seen after massed application of 5-HT, but decreases desensitization during spaced application of 5-HT. We present a mathematical model describing how the molecular components of this signaling pathway are connected and regulated in order to elicit the previously described dynamics. This model contains two proteins differentially produced by massed or spaced training as well as a PKA-dependent cycling step. The model is capable of reproducing experimental observations with high accuracy and makes several predictions on the mechanism of desensitization as well as its long-time behavior. |