Synaptic silencing of fast muscle is compensated by rewired innervation of slow muscle

For decades, numerous studies have proposed that fast muscles contribute to quick movement, while slow muscles underlie locomotion requiring endurance. By generating mutant zebrafish whose fast muscles are synaptically silenced, we examined the contribution of fast muscles in both larval and adult zebrafish. In the larval stage, mutants lacked the characteristic startle response to tactile stimuli: bending of the trunk (C-bend) followed by robust forward propulsion. Unexpectedly, adult mutants with silenced fast muscles showed robust C-bends and forward propulsion upon stimulation. Retrograde labeling revealed that motor neurons genetically programmed to form synapses on fast muscles are instead rerouted and innervate slow muscles, which led to partial conversion of slow and intermediate muscles to fast muscles. Thus, extended silencing of fast muscle synapses changed motor neuron innervation and caused muscle cell type conversion, revealing an unexpected mechanism of locomotory adaptation.