Disruption of Epithalamic Left-Right Asymmetry Increases Anxiety in Zebrafish
Disruption of Epithalamic Left-Right Asymmetry Increases Anxiety in Zebrafish
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DOI：
10.1523/jneurosci.2593-15.2015
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发表时间：
2015-12-02
影响因子：
5.3
通讯作者：
Halpern, Marnie E.
中科院分区：
文献类型：
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作者：
Facchin, Lucilla;Duboue, Erik R.;Halpern, Marnie E.
大脑左右两侧的差异在动物界随处可见，但神经不对称性改变的后果尚不清楚。在斑马鱼的上丘脑中，肾上腺旁区位于大脑左侧，它影响邻近的背缰核（dHb）的发育，导致左侧和右侧dHb的组织、基因表达和连接性不同。左-右（L-R）反转的会阴旁的位置和dHb不对称自发发生在一小部分的人口，而dHb发展对称实验消融后的会阴旁。缰核区域以前被认为与调节小鼠和斑马鱼的恐惧有关，但其L-R不对称性的相关性尚不清楚。我们现在证明，破坏方向性的斑马鱼上丘脑导致减少探索行为和增加皮质醇水平，增强焦虑的迹象。因此，暴露于丁螺环酮（一种抗焦虑药）可显著抑制非典型行为。当它位于大脑右侧时，从会阴旁到dHb的轴突投射变化更大，这表明L-R反转不一定代表神经解剖学的镜像。这些结果突出了方向不对称的上丘脑在调节斑马鱼的应激反应的重要性。
Differences between the left and right sides of the brain are found throughout the animal kingdom, but the consequences of altered neural asymmetry are not well understood. In the zebrafish epithalamus, the parapineal is located on the left side of the brain where it influences development of the adjacent dorsal habenular (dHb) nucleus, causing the left and right dHb to differ in their organization, gene expression, and connectivity. Left-right (L-R) reversal of parapineal position and dHb asymmetry occurs spontaneously in a small percentage of the population, whereas the dHb develop symmetrically following experimental ablation of the parapineal. The habenular region was previously implicated in modulating fear in both mice and zebrafish, but the relevance of its L-R asymmetry is unclear. We now demonstrate that disrupting directionality of the zebrafish epithalamus causes reduced exploratory behavior and increased cortisol levels, indicative of enhanced anxiety. Accordingly, exposure to buspirone, an anxiolytic agent, significantly suppresses atypical behavior. Axonal projections from the parapineal to the dHb are more variable when it is located on the right side of the brain, revealing that L-R reversals do not necessarily represent a neuroanatomical mirror image. The results highlight the importance of directional asymmetry of the epithalamus in the regulation of stress responses in zebrafish.