Molecular blueprints for spinal circuit modules controlling locomotor speed in zebrafish

Abstract

The flexibility of motor actions is ingrained in the diversity of neurons and how they are organized into functional circuit modules, yet our knowledge of the molecular underpinning of motor circuit modularity remains limited. Here we use adult zebrafish to link the molecular diversity of motoneurons (MNs) and the rhythm-generating V2a interneurons (INs) with the modular circuit organization that is responsible for changes in locomotor speed. We show that the molecular diversity of MNs and V2a INs reflects their functional segregation into slow, intermediate or fast subtypes. Furthermore, we reveal shared molecular signatures between V2a INs and MNs of the three speed circuit modules. Overall, by characterizing how the molecular diversity of MNs and V2a INs relates to their function, connectivity and behavior, our study provides important insights not only into the molecular mechanisms for neuronal and circuit diversity for locomotor flexibility but also for charting circuits for motor actions in general.

Synaptic architecture of leg and wing premotor control networks inDrosophila

“…Each preMN tends to make more synapses onto larger MNs, in proportion to the total synaptic input to that MN. The structure we found is fundamentally different from the connectivity of premotor circuits that control MN recruitment and swimming speed in adult zebrafish, where dedicated pools of V2a premotor neurons synapse onto either slow or fast MNs (Pallucchi et al, 2024; Song et al, 2020). This pattern of roughly equal synaptic weights highlights the need for a reciprocal gradient of excitability to ensure that leg MNs are recruited in the correct order.…”

“…The precise synaptic architecture of limb premotor circuits that is responsible for implementing the size principle has remained a mystery since the phenomenon was first described in cat leg muscles over 60 years ago (Henneman, 1957). Recent work in adult zebrafish has revealed that separate populations of interneurons synapse onto small/slow vs. large/fast MNs, raising the question of how common input to a motor pool contributes to the recruitment hierarchy (Pallucchi et al, 2024; Song et al, 2020). In addition, modern muscle recordings in primates demonstrate that the correlations in motor unit firing rates can flexibly change with the demands of the motor task, in contrast to stereotyped recruitment that is the foundation of the size principle (Marshall et al, 2022).…”

The vestibulospinal nucleus is a locus of balance development

“…Evidence in zebrafish also supports the existence of subtypes of vestibulospinal neurons based on sensory afferent input and axon projection type 39 . A key challenge going forward will be identifying transcriptional determinants of subtype identity 70,71 ; such a molecular atlas would allow for effective cross-species comparison of subtype function. Our finding that vestibulospinal neurons coordinate fin and trunk movements thus strengthens the proposal that the vestibulospinal circuit serves fundamentally similar roles across disparate body plans and locomotor strategies.…”