浦肯野细胞控制斑马鱼幼鱼的姿势。

Franziska Auer, Katherine Nardone, Koji Matsuda, Masahiko Hibi, David Schoppik
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引用次数: 0

摘要

小脑功能障碍导致姿势不稳定。最近对自由活动的啮齿类动物的研究改变了小脑对姿势贡献的研究。然而,陆地运动和啮齿动物小脑的复杂性促使人们开发出新的方法来干扰更简单脊椎动物的小脑功能。在这里,我们使用了一种强大的化学遗传学工具(TRPV1/辣椒素)来定义浦肯野细胞——小脑皮层的输出神经元——在幼年斑马鱼自由深入游泳时的作用。我们实现了浦肯野细胞的双向控制(激活和消融),同时对姿势和运动进行了定量高通量评估。激活扰乱了俯仰(上鼻/下鼻)轴的姿势控制。同样,消融破坏了俯仰轴姿势和鳍体协调,导致爬升。姿势破坏在年龄较大的幼虫中更为明显,这为发育中的小脑在控制姿势方面发挥紧急作用提供了一个窗口。最后,我们发现浦肯野细胞的活动可以单独和集体编码倾斜方向,这是姿势控制神经元的一个关键特征。我们的研究结果描绘了小脑在斑马鱼幼体的姿势控制和前庭感觉中的预期作用,确立了TRPV1/辣椒素介导的扰动在一种简单的、遗传上易于处理的脊椎动物中的有效性。此外,通过比较浦肯野细胞消融对姿势的时间贡献,我们发现了小脑在早期发育过程中对姿势的控制。这项工作朝着理解小脑在调节姿势成熟中的祖先作用迈出了重要一步。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Cerebellar Purkinje Cells Control Posture in Larval Zebrafish ( <i>Danio rerio</i> ).

Cerebellar Purkinje Cells Control Posture in Larval Zebrafish ( <i>Danio rerio</i> ).

Cerebellar Purkinje Cells Control Posture in Larval Zebrafish ( <i>Danio rerio</i> ).

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

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

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