Swimming with the current : Fictive locomotion reveals subtle phenotypes in the zebrafish locomotor network

Sammanfattning: Neural networks are the functional building blocks of the central nervous system. To better understand how these networks develop and operate, we turned to the zebrafish locomotor network, with a focus on subtypes of interneurons expressing dmrt3a and wt1a. These neurons first gained interest when a mutation in the Dmrt3 gene was found to be responsible for Icelandic horses’ ability to perform additional gaits, indicating a flexibility within their locomotor central pattern generator.In zebrafish, the Dmrt3 population is known to be commissural, inhibitory and involved in escape behaviors and left-right alternation during locomotion. We characterized the locomotor behavior at embryonic, larval and juvenile stages in dmrt3a mutants. A strong phenotype was observed in larval escape behavior, showing reduced top speed while the animals spent more time accelerating. While the phenotype subdued as the animals developed, juveniles still maintained a lower maximum locomotor speed.To get a more detailed understanding of the observed phenotypes, an experimental setup was established combining dual ventral root recordings with calcium imaging and various sensory stimuli to induce diverse locomotor outputs in fictively behaving larva. Implementing this method, we investigated the function of Dmrt3 and Wt1 expressing interneurons in escape behaviors and found that knock-down of Dmrt3a disturbed the fast phase of tail evoked escapes, while knock-down of Wt1a lead to aberrant looming evoked escapes, indicating sub-functionalization. Finally, calcium imaging was employed to reveal the activity of Dmrt3 neurons at a population level. The fraction of active cells steadily increased during development and small clusters of correlated Dmrt3 interneuron ensembles were observed within a segment. This work provides insights into how parallel motor networks are orchestrated to generate a flexible behavioral output, revealing fundamental principles extending to the workings of our own brain.