Neuronal birthdate reveals topography in a vestibular brainstem circuit for gaze stabilization

Goldblatt, Dena; Huang, Stephanie; Greaney, Marie R.; Hamling, Kyla R.; Voleti, Venkatakaushik; Campos, Citlali Pérez; Patel, Kripa; Li, Wenze; Hillman, Elizabeth M. C.; Bagnall, Martha W.; Schoppik, David

doi:10.1101/2022.10.21.513243

Cited by 6 publications

(33 citation statements)

References 151 publications

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“…Ventral projection neurons receive additional input from the semicircular canals 29 , which encode phasic (fast) tilt sensation. To activate sensory afferents from the semicircular canals, we used TIPM to deliver two impulses of angular rotation (Figure 3A-Figure 3B) 29,41 . We observed no changes in phox2a mutants.…”

Section: Peripheral-to-central Circuit Assembly Does Not Require Moto...mentioning

confidence: 99%

“…The vertebrate vestibulo-ocular reflex circuit consists of three neuron types -peripheral sensory, central projection, and extraocular motor neurons -that stabilize gaze after head/body tilts (Figure 1A) 21 . Subtype fate, anatomical connectivity, and function are inextricably linked: directionally-tuned sensory neurons innervate nose-up/nose-down subtypes of projection neurons, which in turn innervate specific motor neurons that selectively control either eyes-down or eyes-up muscles 3,[22][23][24][25][26][27][28][29] . As both the recipients and origin of directional information, projection neuron fate specification is tantamount to proper circuit assembly.…”

Section: Introductionmentioning

confidence: 99%

“…As both the recipients and origin of directional information, projection neuron fate specification is tantamount to proper circuit assembly. Recent work has established the vertical vestibulo-ocular reflex circuit in zebrafish as a model to uncover determinants of fate and connectivity [24][25][26]29 given the ease of optical imaging, abundant tools for genetic perturbations, rapid development, and robust evolutionary conservation.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Peripheral-to-central Circuit Assembly Does Not Require Moto...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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“…To regulate speed, zebrafish rely on circuits comprised of descending neurons, spinal interneurons, and MNs 25,26,68,69 . Shared functional properties (fast/slow) among cell types within speed control circuits reflect birthdate 25,35,70,71 , similar to other sensorimotor circuits [72][73][74][75][76] . Spatial and temporal morphogen gradients, as well as sequential expression of transcription factors, have been implicated in generating spinal neuron subtype diversity across species 77,78 .…”

Section: Implications For Locomotor Speed Circuit Organization and As...mentioning

confidence: 99%

Determinants of Motor Neuron Functional Subtypes Important for Locomotor Speed

D’Elia

Hameedy

Goldblatt

et al. 2022

Preprint

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Locomotion requires precise control of the strength and speed of muscle contraction and is achieved by recruiting functionally-distinct subtypes of motor neurons (MNs). MNs are essential to movement and differentially susceptible in disease, but little is known about how MNs acquire functional subtype-specific molecular features during development. Using single cell RNA profiling in larval zebrafish, we identify novel and conserved molecular signatures for MN functional subtypes, and identify genes expressed in both early post-mitotic and mature MNs. Assessing MN development in genetic mutants, we define a molecular program essential for MN functional subtype specification. Two evolutionarily-conserved transcription factors, Prdm16 and Evi1, are both functional subtype-specific determinants integral for fast MN development. Loss ofprdm16orevi1causes fast MNs to develop transcriptional profiles and innervation similar to slow MNs. These results reveal the molecular diversity of vertebrate spinal MNs and demonstrate that functional subtypes are specified through intrinsic transcriptional codes.

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“…At 4 days post-fertilization (dpf), larval zebrafish maintain a dorsal-up stable roll posture to navigate in the water column, find food, and avoid predators. To do so, loss-of-function experiments [14][15][16] suggest they rely on a sense of gravity mediated by an otolithic (utricular) organ; while present and capable of transduction 17 , their semicircular canals are too small to function under normal conditions 18 . Larval zebrafish are genetically-tractable and largely transparent, allowing for rapid and reliable identification of vestibulospinal neurons 19,20 .…”

Section: Introductionmentioning

confidence: 99%

The nature and origin of synaptic inputs to vestibulospinal neurons in the larval zebrafish

Hamling

Harmon

Schoppik

2023

Preprint

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Vestibulospinal neurons integrate sensed imbalance to regulate postural reflexes. As an evolutionarily-conserved neural population, understanding their synaptic and circuit-level properties can offer insight into vertebrate anti-gravity reflexes. Motivated by recent work, we set out to verify and extend the characterization of vestibulospinal neurons in the larval zebrafish. Using current clamp recordings together with stimulation, we observed that larval zebrafish vestibulospinal neurons are silent at rest, yet capable of sustained spiking following depolarization. Neurons responded systematically to a vestibular stimulus (translation in the dark); responses were abolished after chronic or acute loss of the utricular otolith. Voltage clamp recordings at rest revealed strong excitatory inputs with a characteristic multimodal distribution of amplitudes, as well as strong inhibitory inputs. Excitatory inputs within a particular mode (amplitude range) routinely violated refractory period criteria and exhibited complex sensory tuning, suggesting a non-unitary origin. Next, using a unilateral loss-of-function approach, we characterized the source of vestibular inputs to vestibulospinal neurons from each ear. We observed systematic loss of high-amplitude excitatory inputs after utricular lesions ipsilateral, but not contralateral to the recorded vestibulospinal neuron. In contrast, while some neurons had decreased inhibitory inputs after either ipsilateral or contralateral lesions, there were no systematic changes across the population of recorded neurons. We conclude that imbalance sensed by the utricular otolith shapes the responses of larval zebrafish vestibulospinal neurons through both excitatory and inhibitory inputs. Our findings expand our understanding of how a vertebrate model, the larval zebrafish, might use vestibulospinal input to stabilize posture. More broadly, when compared to recordings in other vertebrates, our data speak to conserved origins of vestibulospinal synaptic input.

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Neuronal birthdate reveals topography in a vestibular brainstem circuit for gaze stabilization

Cited by 6 publications

References 151 publications

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

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

Determinants of Motor Neuron Functional Subtypes Important for Locomotor Speed

The nature and origin of synaptic inputs to vestibulospinal neurons in the larval zebrafish

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