Effects of myosuppressin, a peptide neuromodulator, on membrane currents in the crustacean cardiac ganglion

Central pattern generators are neural circuits that can independently produce rhythmic patterns of electrical activity without central or periphery inputs. They control rhythmic behaviors like breathing in humans and cardiac activity in crustaceans. Rhythmic behaviors must be flexible to respond appropriately to a changing environment; this flexibility is achieved through the action of neuromodulators. The cardiac ganglion of Homarus americanus, the American lobster, is a central pattern generator made up of four premotor neurons and five motor neurons. Membrane currents in each cell type, which can be targeted for modulation by various molecules, generate rhythmic bursts of action potentials. Myosuppressin, a FMRFamide-like peptide, is one such neuromodulator. The currents targeted for neuromodulation by myosuppressin are unknown. I investigated the molecular and physiological underpinnings of the modulatory effect of myosuppressin on motor neurons in the cardiac ganglion. First, using single cell RT-qPCR, I determined that across animals, motor neurons express myosuppressin receptor subtype II at equal levels relative to each other. Using sharp intracellular recordings, I showed that myosuppressin decreased burst frequency and the rate of depolarization during the inter-burst interval. I predicted that this effect resulted from the modulation of either A-type potassium current or calcium-dependent potassium current. Using two-electrode voltage clamp, I found that total outward current did not substantially change after treatment with myosuppressin. This result was surprising and provides grounds for explorations of subtle forms of neuromodulation in simple neural circuits.