Single-cell RNAseq analysis of spinal locomotor circuitry in larval zebrafish

Identification of the neuronal types that form the specialized circuits controlling distinct behaviors has benefited greatly from the simplicity offered by zebrafish. Electrophysiological studies have shown that in addition to connectivity, understanding of circuitry requires identification of funct...

Full description

Bibliographic Details
Main Authors: Jimmy J Kelly, Hua Wen, Paul Brehm
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2023-11-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/89338
_version_ 1797608922603847680
author Jimmy J Kelly
Hua Wen
Paul Brehm
author_facet Jimmy J Kelly
Hua Wen
Paul Brehm
author_sort Jimmy J Kelly
collection DOAJ
description Identification of the neuronal types that form the specialized circuits controlling distinct behaviors has benefited greatly from the simplicity offered by zebrafish. Electrophysiological studies have shown that in addition to connectivity, understanding of circuitry requires identification of functional specializations among individual circuit components, such as those that regulate levels of transmitter release and neuronal excitability. In this study, we use single-cell RNA sequencing (scRNAseq) to identify the molecular bases for functional distinctions between motoneuron types that are causal to their differential roles in swimming. The primary motoneuron, in particular, expresses high levels of a unique combination of voltage-dependent ion channel types and synaptic proteins termed functional ‘cassettes.’ The ion channel types are specialized for promoting high-frequency firing of action potentials and augmented transmitter release at the neuromuscular junction, both contributing to greater power generation. Our transcriptional profiling of spinal neurons further assigns expression of this cassette to specific interneuron types also involved in the central circuitry controlling high-speed swimming and escape behaviors. Our analysis highlights the utility of scRNAseq in functional characterization of neuronal circuitry, in addition to providing a gene expression resource for studying cell type diversity.
first_indexed 2024-03-11T05:50:21Z
format Article
id doaj.art-8e0c182d09f742978a9f5a92561412b7
institution Directory Open Access Journal
issn 2050-084X
language English
last_indexed 2024-03-11T05:50:21Z
publishDate 2023-11-01
publisher eLife Sciences Publications Ltd
record_format Article
series eLife
spelling doaj.art-8e0c182d09f742978a9f5a92561412b72023-11-17T14:08:34ZengeLife Sciences Publications LtdeLife2050-084X2023-11-011210.7554/eLife.89338Single-cell RNAseq analysis of spinal locomotor circuitry in larval zebrafishJimmy J Kelly0https://orcid.org/0009-0007-5807-0676Hua Wen1https://orcid.org/0009-0009-5326-8741Paul Brehm2https://orcid.org/0000-0001-7804-5258Vollum Institute, Oregon Health & Science University, Portland, United StatesVollum Institute, Oregon Health & Science University, Portland, United StatesVollum Institute, Oregon Health & Science University, Portland, United StatesIdentification of the neuronal types that form the specialized circuits controlling distinct behaviors has benefited greatly from the simplicity offered by zebrafish. Electrophysiological studies have shown that in addition to connectivity, understanding of circuitry requires identification of functional specializations among individual circuit components, such as those that regulate levels of transmitter release and neuronal excitability. In this study, we use single-cell RNA sequencing (scRNAseq) to identify the molecular bases for functional distinctions between motoneuron types that are causal to their differential roles in swimming. The primary motoneuron, in particular, expresses high levels of a unique combination of voltage-dependent ion channel types and synaptic proteins termed functional ‘cassettes.’ The ion channel types are specialized for promoting high-frequency firing of action potentials and augmented transmitter release at the neuromuscular junction, both contributing to greater power generation. Our transcriptional profiling of spinal neurons further assigns expression of this cassette to specific interneuron types also involved in the central circuitry controlling high-speed swimming and escape behaviors. Our analysis highlights the utility of scRNAseq in functional characterization of neuronal circuitry, in addition to providing a gene expression resource for studying cell type diversity.https://elifesciences.org/articles/89338transcriptomicssynaptic transmissionion channelsglial cellneurons
spellingShingle Jimmy J Kelly
Hua Wen
Paul Brehm
Single-cell RNAseq analysis of spinal locomotor circuitry in larval zebrafish
eLife
transcriptomics
synaptic transmission
ion channels
glial cell
neurons
title Single-cell RNAseq analysis of spinal locomotor circuitry in larval zebrafish
title_full Single-cell RNAseq analysis of spinal locomotor circuitry in larval zebrafish
title_fullStr Single-cell RNAseq analysis of spinal locomotor circuitry in larval zebrafish
title_full_unstemmed Single-cell RNAseq analysis of spinal locomotor circuitry in larval zebrafish
title_short Single-cell RNAseq analysis of spinal locomotor circuitry in larval zebrafish
title_sort single cell rnaseq analysis of spinal locomotor circuitry in larval zebrafish
topic transcriptomics
synaptic transmission
ion channels
glial cell
neurons
url https://elifesciences.org/articles/89338
work_keys_str_mv AT jimmyjkelly singlecellrnaseqanalysisofspinallocomotorcircuitryinlarvalzebrafish
AT huawen singlecellrnaseqanalysisofspinallocomotorcircuitryinlarvalzebrafish
AT paulbrehm singlecellrnaseqanalysisofspinallocomotorcircuitryinlarvalzebrafish