Determinants of motor neuron functional subtypes important for locomotor speed

D’Elia, Kristen P.; Hameedy, Hanna; Goldblatt, Dena; Frazel, Paul; Kriese, Mercer; Zhu, Yunlu; Hamling, Kyla R.; Kawakami, Koichi; Liddelow, Shane A.; Schoppik, David; Dasen, Jeremy S.

doi:10.1016/j.celrep.2023.113049

Cited by 25 publications

(10 citation statements)

References 104 publications

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“…Although, in mice, MN subtypes were not segregated into different clusters, some known marker genes related to slow versus fast were enriched in different neurons within the same cluster 27 . Recent studies in embryonic and larval zebrafish used single-cell RNA profiling to identify molecular signatures for MN subtypes and their specification at early developmental stages 28 , 45 . Our study in adult zebrafish reveals that the three subtypes of functionally defined MNs (slow, intermediate and fast) are delineated by distinct molecular features and identified several additional molecular markers for slow, intermediate and fast MNs that could be used to guide studies in mammals.…”

Section: Discussionmentioning

confidence: 99%

Molecular blueprints for spinal circuit modules controlling locomotor speed in zebrafish

Pallucchi,

Bertuzzi,

Madrid

et al. 2023

Nat Neurosci

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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.

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Section: Discussionmentioning

confidence: 99%

Molecular blueprints for spinal circuit modules controlling locomotor speed in zebrafish

Pallucchi,

Bertuzzi,

Madrid

et al. 2023

Nat Neurosci

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“…These results extend our original report where a lower-throughput method (photoablation) suggested that Purkinje cell loss impacted the fintrunk relationship. In larval zebrafish, the neuronal substrates for axial speed control [72][73][74][75][76][77] and fin engagement 78 are known. The potential for whole-brain imaging in larval zebrafish 35 , particularly with high-speed voltage indicators 79 and cutting-edge modeling approaches 80 , stands to reveal how Purkinje cell activity comes to coordinate body and fin movements.…”

Section: Contributions Of Purkinje Cells To Posturementioning

confidence: 99%

Cerebellar Purkinje Cells Control Posture in Larval Zebrafish (Danio rerio)

Auer,

Nardone,

Matsuda

et al. 2023

Preprint

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Cerebellar dysfunction leads to postural instability. Recent work in freely moving rodents has transformed investigations of cerebellar contributions to posture. However, the combined complexity of terrestrial locomotion and the rodent cerebellum motivate development of new approaches to perturb cerebellar function in simpler vertebrates. Here, we used a powerful chemogenetic tool (TRPV1/capsaicin) to define the role of Purkinje cells — the output neurons of the cerebellar cortex — as larval zebrafish swam freely in depth. We achieved both bidirectional control (activation and ablation) of Purkinje cells while performing quantitative high-throughput assessment of posture and locomotion. Activation disrupted postural control in the pitch (nose-up/nose-down) axis. Similarly, ablations disrupted pitch-axis posture and fin-body coordination responsible for climbs. Postural disruption was more pronounced in older larvae, offering a window into emergent roles for the developing cerebellum in the control of posture. Finally, we found that activity in Purkinje cells could individually and collectively encode tilt direction, a key feature of postural control neurons. Our findings delineate an expected role for the cerebellum in postural control and vestibular sensation in larval zebrafish, establishing the validity of TRPV1/capsaicin-mediated perturbations in a simple, genetically-tractable vertebrate. Moreover, by comparing the contributions of Purkinje cell ablations to posture in time, we uncover signatures of emerging cerebellar control of posture across early development. This work takes a major step towards understanding an ancestral role of the cerebellum in regulating postural maturation.

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“…Fate in the vestibulo-ocular reflex circuit follows from connectivity 21 , but neuronal fate can also be defined with respect to unique transcriptional signatures. Previously, we developed a sequencing pipeline to discover transcription factors that specify functional subtypes of spinal motor neurons and evaluate the consequences of perturbations on transcriptional fate 47 . We adapted this approach to determine if loss of motor-derived signals changed the transcriptional profiles of projection neurons.…”

Section: Resultsmentioning

confidence: 99%

Motor neurons are dispensable for the assembly of a sensorimotor circuit for gaze stabilization

Goldblatt,

Rosti,

Hamling

et al. 2024

Preprint

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Sensorimotor reflex circuits engage distinct neuronal subtypes, defined by precise connectivity, to transform sensation into compensatory behavior. Whether and how motor neuron populations specify the subtype fate and/or sensory connectivity of their pre-motor partners remains controversial. Here, we discovered that motor neurons are dispensable for proper connectivity in the vestibular reflex circuit that stabilizes gaze. We first measured activity following vestibular sensation in pre-motor projection neurons after constitutive loss of their extraocular motor neuron partners. We observed normal responses and topography indicative of unchanged functional connectivity between sensory neurons and projection neurons. Next, we show that projection neurons remain anatomically and molecularly poised to connect appropriately with their downstream partners. Lastly, we show that the transcriptional signatures that typify projection neurons develop independently of motor partners. Our findings comprehensively overturn a long-standing model: that connectivity in the circuit for gaze stabilization is retrogradely determined by motor partner-derived signals. By defining the contribution of motor neurons to specification of an archetypal sensorimotor circuit, our work speaks to comparable processes in the spinal cord and advances our understanding of general principles of neural development.

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Determinants of motor neuron functional subtypes important for locomotor speed

Cited by 25 publications

References 104 publications

Molecular blueprints for spinal circuit modules controlling locomotor speed in zebrafish

Molecular blueprints for spinal circuit modules controlling locomotor speed in zebrafish

Cerebellar Purkinje Cells Control Posture in Larval Zebrafish (Danio rerio)

Motor neurons are dispensable for the assembly of a sensorimotor circuit for gaze stabilization

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