Modeling spinal locomotor circuits for movements in developing zebrafish

Many spinal circuits dedicated to locomotor control have been identified in the developing zebrafish. How these circuits operate together to generate the various swimming movements during development remains to be clarified. In this study, we iteratively built models of developing zebrafish spinal circuits coupled to simplified musculoskeletal models that reproduce coiling and swimming movements. The neurons of the models were based upon morphologically or genetically identified populations in the developing zebrafish spinal cord. We simulated intact spinal circuits as well as circuits with silenced neurons or altered synaptic transmission to better understand the role of specific spinal neurons. Analysis of firing patterns and phase relationships helped to identify possible mechanisms underlying the locomotor movements of developing zebrafish. Notably, our simulations demonstrated how the site and the operation of rhythm generation could transition between coiling and swimming. The simulations also underlined the importance of contralateral excitation to multiple tail beats. They allowed us to estimate the sensitivity of spinal locomotor networks to motor command amplitude, synaptic weights, length of ascending and descending axons, and firing behavior. These models will serve as valuable tools to test and further understand the operation of spinal circuits for locomotion. eLife digest The spinal cord is a column of nerve tissue that connects the brain to the rest of the body in vertebrate animals. Nerve cells in the spinal cord, called neurons, help to control and coordinate the body's movements. As the spinal cord develops, new neurons are born and new connections are made between neurons and muscles, resulting in more coordinated and skillful movements as time goes on. Zebrafish, for example, display body-bending maneuvers called coils within 24 hours of the egg being fertilized. Next, bursts of swimming movements emerge, which are driven by sporadic tail beats. These tail maneuvers become more consistent as the fish develops, and eventually result in smooth movements called beat-and-glide swimming. The groups of spinal cord neurons that appear at each stage of zebrafish development have been characterized, but it remains unclear how newly formed circuits (groups of neurons recently connected to each other) work together to produce swimming maneuvers. To answer this question, Roussel et al. simulated changes in the spinal cord that help zebrafish acquire new swimming movements as they grow. The computer models encoded neural circuits based on cell populations identified in experimental studies, and replicated swimming behaviors that emerge during the first few days of zebrafish development. Simulations tested how specific neural circuits generate the characteristic swimming movements that represent key developmental milestones in zebrafish. The results showed that adding new neurons and more cell-to-cell connections led to increasingly sophisticated swimming maneuvers. As the zebrafish spinal cord matured, the fish were better able to control the pace and duration of their swimming movements. Roussel et al. also identified specific patterns of neural activity linked to particular maneuvers. For example, tail beats switch direction when neurons on one side of the spinal cord excite neurons on the opposite side. This activity, which becomes more rhythmic, also needs to be exquisitely timed to produce and coordinate the right motion. Roussel et al.'s modelling of developmental milestones in growing zebrafish provides insights into how neural networks control movement. The computer models are among the first to accurately reproduce swimming behaviors in developing zebrafish. More experimental data could be added to the models to capture the full range of early zebrafish movements, and to further investigate how maturing spinal cord circuits control swimming. Since zebrafish and mammals have many spinal neurons in common, further research may aid our understanding of movement disorders in humans.