Pharmacological modulation of the M-current shapes locomotor function in developing zebrafish

The M-current (I_M) is a non-inactivating potassium current that has been implicated in the control of locomotion in mammals, where it was shown to shape the rhythm governing locomotor movements. We tested whether I_M might also be involved in the control of locomotor movements in developing zebrafish. Specifically, we investigated the involvement of I_M in the execution of escape responses and swimming movement of zebrafish aged 4-5 days post-fertilization (dpf) using XE-991and ICA-069673, a pharmacological blocker and enhancer of I_M, respectively. We found that I_M may influence the number and type of swim bouts in an escape response but not the duration of the first bout nor the tail beat frequency. Enhancing I_M reduced the distance swam with slow or fast swimming maneuvers by freely behaving larval zebrafish. We then studied whether I_M is involved in locomotor output by spinal circuits using various approaches to induce motor activity in spinalized 4-5 dpf zebrafish. We found that while modulating I_M during NMDA-evoked swimming activity had negligible effects, modulating I_M during swimming activity evoked by a generalized depolarization of the spinal cord affected specific swimming parameters. In particular, XE-991 and ICA-069673 had opposite effects on overall spiking activity, swimming episode frequency and duration, and the number of bursts within each episode. In summary, I_M was found to be involved in certain facets of escape response and swimming in larval zebrafish, and some of this influence resides within the expression of this current in spinal circuits.