Environmental and Molecular Modulation of Motor Individuality in Larval Zebrafish.

Environmental and Molecular Modulation of Motor Individuality in Larval Zebrafish.
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DOI:
10.3389/fnbeh.2021.777778
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发表时间:
2021
影响因子:
3
通讯作者:
Horstick EJ
Horstick EJ
中科院分区:
医学3区
文献类型:
--
作者:
Hageter J;Waalkes M;Starkey J;Copeland H;Price H;Bays L;Showman C;Laverty S;Bergeron SA;Horstick EJ

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先天的行为偏差,如人类的用手习惯,是一种普遍存在的个体间变异形式,并不是严格地固定在基因组中,而是受到各种内部和外部线索的影响。然而,调节行为变异的遗传和环境因素仍然知之甚少,特别是在脊椎动物中。为了确定影响行为变异的遗传和环境因素,我们利用斑马鱼幼虫的光搜索行为。在光搜索过程中,个体会优先选择方向性偏置,这种偏置是持续的,并且是不可遗传的。我们以前的工作表明,偏见是由缰-喙PT电路和Notch信号相关的基因。在这里,我们使用一个中等吞吐量的记录策略和无偏分析表明,显着的个体间的差异存在于野生型斑马鱼幼虫转向偏好。我们分类稳定的左,右,无偏转向类型,大多数人表现出方向偏好。我们表明,无偏见的行为是由于光响应的损失,但减少了持久性在同一方向转向。在升高的温度下饲养幼虫选择性地减少了翻转类型和影响喙PT神经元,特别是。暴露于同种,可变盐度,环境富集,和物理干扰并没有显着影响个体间的转向偏差。Notch信号传导的药理学操作以剂量依赖性方式破坏缰发育并转变偏好个体性,从而确立Notch信号传导的直接作用。最后,已知的Notch途径影响基因gsx 2的突变等位基因破坏了转向偏好个性,暗示独立于先前建立的缰-喙PT的大脑区域可能有助于个体间变异。这些结果表明,斑马鱼幼虫是一个强大的脊椎动物模型,与建立的神经靶标显示出对特定的环境和基因信号中断的敏感性,个体间的变化。我们的研究结果为脊椎动物神经系统中的变异是如何产生的提供了新的见解。
Innate behavioral biases such as human handedness are a ubiquitous form of inter-individual variation that are not strictly hardwired into the genome and are influenced by diverse internal and external cues. Yet, genetic and environmental factors modulating behavioral variation remain poorly understood, especially in vertebrates. To identify genetic and environmental factors that influence behavioral variation, we take advantage of larval zebrafish light-search behavior. During light-search, individuals preferentially turn in leftward or rightward loops, in which directional bias is sustained and non-heritable. Our previous work has shown that bias is maintained by a habenula-rostral PT circuit and genes associated with Notch signaling. Here we use a medium-throughput recording strategy and unbiased analysis to show that significant individual to individual variation exists in wildtype larval zebrafish turning preference. We classify stable left, right, and unbiased turning types, with most individuals exhibiting a directional preference. We show unbiased behavior is not due to a loss of photo-responsiveness but reduced persistence in same-direction turning. Raising larvae at elevated temperature selectively reduces the leftward turning type and impacts rostral PT neurons, specifically. Exposure to conspecifics, variable salinity, environmental enrichment, and physical disturbance does not significantly impact inter-individual turning bias. Pharmacological manipulation of Notch signaling disrupts habenula development and turn bias individuality in a dose dependent manner, establishing a direct role of Notch signaling. Last, a mutant allele of a known Notch pathway affecter gene, gsx2, disrupts turn bias individuality, implicating that brain regions independent of the previously established habenula-rostral PT likely contribute to inter-individual variation. These results establish that larval zebrafish is a powerful vertebrate model for inter-individual variation with established neural targets showing sensitivity to specific environmental and gene signaling disruptions. Our results provide new insight into how variation is generated in the vertebrate nervous system.
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