Single-cell RNAseq analysis of spinal locomotor circuitry in larval zebrafish.
Single-cell RNAseq analysis of spinal locomotor circuitry in larval zebrafish.
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DOI：
10.7554/elife.89338
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发表时间：
2023-11-17
期刊：
影响因子：
7.7
通讯作者：
Brehm P
中科院分区：
文献类型：
--
作者：
Kelly JJ;Wen H;Brehm P
识别形成控制不同行为的特殊回路的神经元类型，很大程度上得益于斑马鱼提供的简单性。电生理学研究表明，除了连通性之外，对电路的理解还需要识别单个电路组件之间的功能专门化，例如那些调节递质释放水平和神经元兴奋性的组件。在这项研究中，我们使用单细胞RNA测序（scRNAseq）来鉴定运动神经元类型之间功能差异的分子基础，这些功能差异导致了它们在游泳中的不同作用。特别是初级运动神经元，表达高水平的电压依赖性离子通道类型和被称为功能“磁带”的突触蛋白的独特组合。“离子通道类型专门用于促进动作电位的高频放电和增强神经肌肉连接处的递质释放，两者都有助于产生更大的能量。”我们对脊髓神经元的转录谱分析进一步将这种磁带的表达分配给特定的中间神经元类型，这些中间神经元类型也参与控制高速游泳和逃避行为的中央电路。我们的分析强调了scRNAseq在神经回路功能表征中的效用，除了为研究细胞类型多样性提供基因表达资源之外。
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.
影响因子：
4.3
作者：
Yang L;Wang F;Strähle U
通讯作者：
Strähle U
影响因子：
8.8
作者：
Pallucchi, Irene;Bertuzzi, Maria;Michel, Jennifer Carlisle;Miller, Adam C.;El Manira, Abdeljabbar
通讯作者：
El Manira, Abdeljabbar