Single-cell transcriptomic profiling of the zebrafish inner ear reveals molecularly distinct hair cell and supporting cell subtypes

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Jan. 4, 2023

A major cause of human deafness and vestibular dysfunction is permanent loss the mechanosensory hair cells inner ear. In non-mammalian vertebrates such as zebrafish, regeneration missing can occur throughout life. While a comparative approach has potential to reveal basis differential regenerative ability, degree which ears fish mammals share common supporting cell types remains unresolved. Here, we perform single-cell RNA sequencing zebrafish ear at embryonic through adult stages catalog diversity non-sensory cells. We identify putative progenitor population for cells, well distinct in maculae versus cristae. The differ from those described lateral line system, distributed organ most studies have been conducted. maculae, two subtypes that gene expression with mammalian striolar or extrastriolar situ hybridization reveals these occupy spatial domains within three macular organs, utricle, saccule, lagena, consistent reported electrophysiological properties domains. These findings suggest primitive specialization spatially likely arose last ancestor mammals. similarities type composition between validate relevant model understanding ear-specific function regeneration.

Language: Английский

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Automated synapse-level reconstruction of neural circuits in the larval zebrafish brain

Nature Methods, Journal Year: 2022, Volume and Issue: 19(11), P. 1357 - 1366

Published: Oct. 24, 2022

Abstract Dense reconstruction of synaptic connectivity requires high-resolution electron microscopy images entire brains and tools to efficiently trace neuronal wires across the volume. To generate such a resource, we sectioned imaged larval zebrafish brain by serial block-face at voxel size 14 × 25 nm 3 . We segmented resulting dataset with flood-filling network algorithm, automated detection chemical synapses validated results comparisons transmission microscopic light-microscopic reconstructions. Neurons their connections are stored in form queryable expandable digital address book. reconstructed 208 neurons involved visual motion processing, most them located pretectum, which had been functionally characterized same specimen two-photon calcium imaging. Moreover, mapped all 407 presynaptic postsynaptic partners two superficial interneurons tectum. The resource developed here serves as foundation for synaptic-resolution circuit analyses nervous system.

Language: Английский

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Mechanotransduction in mammalian sensory hair cells

Molecular and Cellular Neuroscience, Journal Year: 2022, Volume and Issue: 120, P. 103706 - 103706

Published: Feb. 23, 2022

In the inner ear, auditory and vestibular systems detect translate sensory information regarding sound balance. The cells that transform mechanical input into an electrical signal in these are called hair cells. A specialized organelle on apical surface of bundle detects signals. Displacement causes mechanotransduction channels to open. morphology organization bundle, as well properties characteristics process, differ between different cell types systems. These differences likely contribute maximizing transduction specific signals each system. This review will discuss molecules essential for focusing our attention recent data

Language: Английский

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Determinants of motor neuron functional subtypes important for locomotor speed

Cell Reports, Journal Year: 2023, Volume and Issue: 42(9), P. 113049 - 113049

Published: Sept. 1, 2023

Locomotion requires precise control of the strength and speed muscle contraction is achieved by recruiting functionally distinct subtypes motor neurons (MNs). MNs are essential to movement differentially susceptible in disease, but little known about how acquire functional subtype-specific features during development. Using single-cell RNA profiling embryonic larval zebrafish, we identify novel conserved molecular signatures for MN genes expressed both early post-mitotic mature MNs. Assessing development genetic mutants, define a program subtype specification. Two evolutionarily transcription factors, Prdm16 Mecom, determinants integral fast Loss prdm16 or mecom causes develop transcriptional profiles innervation similar slow These results reveal diversity vertebrate axial demonstrate that specified through intrinsic codes.

Language: Английский

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Spinal Interneurons: Diversity and Connectivity in Motor Control

Annual Review of Neuroscience, Journal Year: 2023, Volume and Issue: 46(1), P. 79 - 99

Published: Feb. 28, 2023

The spinal cord is home to the intrinsic networks for locomotion. An animal in which has been fully severed from brain can still produce rhythmic, patterned locomotor movements as long some excitatory drive provided, such physical, pharmacological, or electrical stimuli. Yet it remains a challenge define underlying circuitry that produces these because contains wide variety of neuron classes whose patterns interconnectivity are poorly understood. Computational models locomotion accordingly rely on untested assumptions about network element identity and connectivity. In this review, we consider neurons, their interconnectivity, significance circuit connections along axis cord. We suggest several lines analysis move toward definitive understanding network.

Language: Английский

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Convergence of vestibular and proprioceptive signals in the cerebellar nodulus/uvula enhances the encoding of self-motion in primates

Current Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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

Current Biology, Journal Year: 2023, Volume and Issue: 33(7), P. 1265 - 1281.e7

Published: March 15, 2023

Across the nervous system, neurons with similar attributes are topographically organized. This topography reflects developmental pressures. Oddly, vestibular (balance) nuclei thought to be disorganized. By measuring activity in birthdated neurons, we revealed a functional map within central projection nucleus that stabilizes gaze larval zebrafish. We first discovered both somatic position and stimulus selectivity follow neuron birthdate. Next, electron microscopy loss-of-function assays, found patterns of peripheral innervation were similarly organized by Finally, birthdate spatial axonal arborization synapse formation outputs. Collectively, find development reveals previously hidden organization input, processing, output layers highly conserved vertebrate sensorimotor circuit. The temporal uncover constrain mechanisms may specify fate, function, vestibulo-ocular reflex neurons. More broadly, our data suggest that, like invertebrates, assemble architecture.

Language: Английский

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Predicting modular functions and neural coding of behavior from a synaptic wiring diagram

Nature Neuroscience, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 22, 2024

A long-standing goal in neuroscience is to understand how a circuit's form influences its function. Here, we reconstruct and analyze synaptic wiring diagram of the larval zebrafish brainstem predict key functional properties validate them through comparison with physiological data. We identify modules strongly connected neurons that turn out be specialized for different behavioral functions, control eye body movements. The movement module further organized into two three-block cycles support positive feedback long hypothesized underlie low-dimensional attractor dynamics oculomotor control. construct neural network model based directly on reconstructed makes predictions cellular-resolution coding position dynamics. These are verified statistically calcium imaging-based activity recordings. This work demonstrates connectome-based brain modeling can reveal previously unknown anatomical structure circuit provide insights linking authors determine vertebrate behaviorally associated modules. this connectome predicts imaging

Language: Английский

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Vestibular physiology and function in zebrafish

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: April 18, 2023

The vestibular system of the inner ear provides information about head motion and spatial orientation relative to gravity ensure gaze stability, balance, postural control. Zebrafish, like humans, have five sensory patches per that serve as peripheral organs, with addition lagena macula neglecta. zebrafish can be easily studied due its accessible location, transparent tissue larval fish, early development behaviors. Thus, are an excellent model for studying development, physiology, function system. Recent work has made great strides elucidate neural circuitry in tracing transmission from receptors periphery central computational circuits driving reflexes. Here we highlight recent illuminates functional organization epithelia, innervating first-order afferent neurons, second-order neuronal targets hindbrain. Using a combination genetic, anatomical, electrophysiological, optical techniques, these studies probed roles signals fish gaze, postural, swimming We discuss remaining questions tractable model.

Language: Английский

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The Nature and Origin of Synaptic Inputs to Vestibulospinal Neurons in the Larval Zebrafish

eNeuro, Journal Year: 2023, Volume and Issue: 10(6), P. ENEURO.0090 - 23.2023

Published: June 1, 2023

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

Language: Английский

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