Quantification of the glial calcium wave leading to motor arrest via sustained activation of noradenergic neurons in larval zebrafish

When an animal faces a threat the usual response is fight or flight. However when the intensity of the danger is inescapable, motor arrest is observed across species: the animal becomes fully immobile and plays dead. The circuit mechanisms underlying this motor arrest are not fully understood. Optical and genetic accessibility makes larval zebrafish an ideal model to investigate this question. Combination of optogenetic methods with data analysis of larval zebrafish recordings has shown that a massive glial calcium wave travels through the body of the fish, disrupting motor circuits and immobilizing the animal [1]. Sustained optogenetic activation of noradrenergic neurons induces motor arrest which is concomitant with a massive glial calcium wave that travels throughout the brain of the animal [1,2]. Nevertheless the dynamical properties of this wave and the interaction between neuron and glia, responsible for the motor arrest, have not yet been thoroughly investigated. Our analysis of calcium recordings of the glial wave show that the hindbrain of the fish is the primal locus involved. An analysis of mean squared displacements differentiates two dynamical regimes of the wave which coincide with a propagation and a decay. We show that wave propagation is superdiffusive in the 30s after the optogenetic stimulation, while decay back to baseline (from 30s to 60s) is mostly diffusive. Finally, to understand how the glial wave impacts the activity of the neurons, we analyze neuronal calcium recordings during wave induction and motor arrest. We conclude that the glial wave disrupts the motor circuits at the level of motor command neurons (vsx2), which had previously been shown to be responsible for motion initiation [3]. Our work gives a comprehensive picture of the cascade of events leading to motor arrest, and sheds light on the complicated interaction between glia and neurons.

References

[1] Mu Y. et al., Cell 178, 27–43.e19 (2019).

[2] Chen A.B. et al., Science 388, 769–775 (2025).

[3] Wyart C. et al., Research Square (2025), https://doi.org/10.21203/rs.3.rs-7216842/v1.