Diving into the zebrafish brain: exploring neuroscience frontiers with genetic tools, imaging techniques, and behavioral insights

Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: March 12, 2024

The zebrafish ( Danio rerio ) is increasingly used in neuroscience research. Zebrafish are relatively easy to maintain, and their high fecundity makes them suitable for high-throughput experiments. Their small, transparent embryos larvae allow microscopic imaging of the developing brain. also share a degree genetic similarity with humans, amenable manipulation techniques, such as gene knockdown, knockout, or knock-in, which allows researchers study role specific genes relevant human brain development, function, disease. can serve model behavioral studies, including locomotion, learning, social interactions. In this review, we present state-of-the-art methods function zebrafish, tools labeling single neurons neuronal circuits, live neural activity, synaptic dynamics protein interactions brain, optogenetic manipulation, use virtual reality technology testing. We highlight potential research, especially regarding genetic-based disorders discuss its certain limitations model.

Language: Английский

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The vestibulospinal nucleus is a locus of balance development

Journal of Neuroscience, Journal Year: 2024, Volume and Issue: 44(30), P. e2315232024 - e2315232024

Published: May 22, 2024

Mature vertebrates maintain posture using vestibulospinal neurons that transform sensed instability into reflexive commands to spinal motor circuits. Postural stability improves across development. However, due the complexity of terrestrial locomotion, contributions postural refinement in early life remain unexplored. Here we leveraged relative simplicity underwater locomotion quantify consequences losing during development larval zebrafish undifferentiated sex. By comparing at two timepoints, discovered later lesions led greater instability. Analysis thousands individual swim bouts revealed disrupted movement timing and corrective reflexes without impacting kinematics, this effect was particularly strong older larvae. Using a generative model swimming, showed how these disruptions could account for increased variability both timepoints. Finally, late fin/trunk coordination observed larvae, linking control schemes used navigate depth. Since were considerably more disruptive stability, conclude balance increase as larvae mature. Vestibulospinal are highly conserved vertebrates; therefore propose they substrate developmental improvements control.

Language: Английский

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Medial and lateral vestibulospinal projections to the cervical spinal cord of the squirrel monkey

Frontiers in Neurology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 3, 2025

The brainstem vestibular nuclei neurons receive synaptic inputs from inner ear acceleration-sensing hair cells, cerebellar output neurons, and ascending signals spinal proprioceptive-related neurons. lateral (LVST) medial (MVST) vestibulospinal (VS) tracts convey their coded to the circuits rapidly counter externally imposed perturbations facilitate stability provide a framework for self-generated head movements. present study describes morphological characteristics of intraaxonally recorded labeled VS monosynaptically connected 8th nerve. visualization axon location in descending longitudinal fasciculus (MLF) differentiated ipsi- (i) contralateral (c)-projecting MVST Vestibuloocular collic (VOC) were comparably typed as cMVST cells but also antidromically activated rostral MLF. Cervical-only LVST projected ipsilaterally ventrolateral funiculi. Targets axons, such central cervical nucleus sternocleidomastoid, trapezius, splenius motoneurons, identified using anti- orthodromic electrical stimuli intra-somatically describe local morphology. Thirty-five (26% 134 attempted samples) successfully permit moderate (near) complete reconstruction trajectories innervations. VOC exhibited prolific innervation caudal nuclei, extensively innervated laminae VII VIII, and, lesser extent, ventromedial lamina IX, C1 C8, on average issued 15 branches along trajectory with 92 terminal en passant boutons per branch. was either uniformly distributed among segments, indicating more global control neck movement, or restricted specific precise motor strategy. pattern iMVST axons resembled that less extensive supplied mostly upper two segments. predominantly equally weighted separate joint moto- inter-neuronal trajectory. Their branching distribution ventral horn provides redundant variable input cell groups. This suggests common site-specific reflexes.

Language: Английский

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A brainstem circuit for gravity-guided vertical navigation

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 13, 2024

ABSTRACT The sensation of gravity anchors our perception the environment and is crucial for navigation. However, neural circuits that transform into commands navigation are undefined. We first determined larval zebrafish ( Danio rerio ) navigate vertically by maintaining a consistent heading across series upward climb or downward dive bouts. Gravity-blind mutant fish swim with more variable excessive veering, leading to inefficient vertical After targeted photoablation ascending vestibular neurons spinal projecting midbrain neurons, but not vestibulospinal was impaired. These data define sensorimotor circuit uses evolutionarily-conserved brainstem architecture gravitational signals persistent work lays foundation understand how inputs allow animals move efficiently through their environment.

Language: Английский

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

Published: Jan. 24, 2025

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

Language: Английский

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Cerebellar Purkinje cells control posture in larval zebrafish (Danio rerio)

eLife, Journal Year: 2025, Volume and Issue: 13

Published: April 3, 2025

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

Language: Английский

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Defects in exosome biogenesis are associated with sensorimotor defects in zebrafishvps4amutants

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 14, 2024

Mutations in human VPS4A are associated with neurodevelopmental defects, including motor delays and defective muscle tone. encodes a AAA-ATPase that is required for membrane scission, but how mutations lead to impaired control of function not known. Here we identified mutation zebrafish vps4a , T248I, affects sensorimotor transformation. In biochemical experiments show the T248I reduces ATPase activity Vps4a disassembly its substrate, ESCRT filaments, which mediate scission. Consistent established role endocytic pathway exosome biogenesis, mutants have enlarged endosomal compartments CNS decreased numbers circulating exosomes. Resembling central form hypotonia patients, neurons cells unaffected mutant as touch sensitivity intact. Unlike somatosensory function, optomotor responses, vestibulospinal (VS), acoustic startle reflexes severely mutants, indicating greater these circuits mutation. ERG recordings indicate visual ability largely reduced however, vivo imaging tone-evoked responses inner ear ascending auditory comparable activity. Further investigation pathways revealed sensory cues failed fully activate VS medial longitudinal fasciculus (MLF) nuclei directly innervate neurons. Our results suggest defect transformation underlies profound yet selective effects on resulting from loss scission mediated by Vps4a.

Language: Английский

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Multisensory strategies for postural compensation after lateral line loss

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 24, 2024

To control elevation underwater, aquatic vertebrates integrate multisensory information (e.g., vestibular, visual, proprioceptive) to guide posture and swim kinematics. Here we characterized how larval zebrafish changed locomotive strategies after imposed instability (decreased buoyancy) in the presence absence of visual cues. We discovered that larvae sank more acute loss lateral line (flow-sensing) hair cells. In response, engaged different compensatory strategies, depending on whether they were light or dark. dark, swam frequently, engaging their trunk steer nose up climb effectively. However, light, climbed often, both pectoral fins elevate. conclude sense use vestibular as available trajectory. Our work is a step towards understanding neural computations responsible for allow orientation navigation depth.

Language: Английский

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Evolutionarily conserved brainstem architecture enables gravity-guided vertical navigation

PLoS Biology, Journal Year: 2024, Volume and Issue: 22(11), P. e3002902 - e3002902

Published: Nov. 12, 2024

The sensation of gravity anchors our perception the environment and is important for navigation. However, neural circuits that transform into commands navigation are undefined. We first determined larval zebrafish ( Danio rerio ) navigate vertically by maintaining a consistent heading across series upward climb or downward dive bouts. Gravity-blind mutant fish swim with more variable excessive veering, leading to less effective vertical After targeted photoablation ascending vestibular neurons spinal projecting midbrain neurons, but not vestibulospinal was impaired. These data define sensorimotor circuit uses evolutionarily conserved brainstem architecture gravitational signals persistent work lays foundation understand how inputs allow animals move effectively through their environment.

Language: Английский

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The vestibulospinal nucleus is a locus of balance development

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 7, 2023

ABSTRACT Mature vertebrates maintain posture using vestibulospinal neurons that transform sensed instability into reflexive commands to spinal motor circuits. Postural stability improves across development. However, due the complexity of terrestrial locomotion, contributions postural refinement in early life remain unexplored. Here we leveraged relative simplicity underwater locomotion quantify consequences losing during development larval zebrafish undifferentiated sex. By comparing at two timepoints, discovered later lesions led greater instability. Analysis thousands individual swim bouts revealed disrupted movement timing and corrective reflexes without impacting kinematics, this effect was particularly strong older larvae. Using a generative model swimming, showed how these disruptions could account for increased variability both timepoints. Finally, late fin/trunk coordination observed larvae, linking control schemes used navigate depth. Since were considerably more disruptive stability, conclude balance increase as larvae mature. Vestibulospinal are highly conserved vertebrates; therefore propose they substrate developmental improvements control. SIGNIFICANCE STATEMENT Many animals experience life. use corrections. To understand if/how shape development, ablated them developmentally important timepoints zebrafish. Loss specific stabilizing behaviors (swim timing, tilt correction, fin/body coordination) profoundly fish. We happens part by changes — significant step towards understanding developing brains gain ability balance.

Language: Английский

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