Modeling the tail-to-limb-based swimming transition in the Xenopus frog

Xenopus frog metamorphosis offers a unique opportunity to study motor circuit changes as tadpoles transition from tail-based undulatory swimming to synchronous limb-based movements. Xenopus motor circuits change at a cellular level and generate different motor patterns over development, but the mechanisms driving the changes in motor output during metamorphosis are not well understood.Here, we combine behavioral analysis with computational modeling. We first quantify swimming (tadpole and frog) behavior using the tracking software SLEAP, measuring the decrease in frequency of tail movement, and the corresponding increase in limb range and coordination, as limbs begin to move synchronously. Next, using adaptive integrate-and-fire (AdEx) neurons, we generate a spinal circuit model based on known cell types and properties. Simulation-based inference is used to optimize neuron parameters and synaptic weights in the spinal circuit model to match physiological recordings of Xenopus tadpole spinal neurons during swimming before and after metamorphosis. Additionally, we can fit the model to match the performance of particular mutants, such as e.g., En1, to evaluate the contribution of specific cell types to motor output. To better decipher the output of our spinal circuit model and provide a basis for comparison to our behavioral recordings, we build a virtual biomechanical tadpole, driven by incoming spikes from the motor neurons of the spinal circuit model. When controlled by spinal circuit model output, the biomechanical model produces swimming activity that allows us to explore the effects of altered circuit composition and connectivity, and compare the output with our behavioral analysis.