Identification of the Zebrafish Ventral Habenula As a Homolog of the Mammalian Lateral Habenula
Identification of the Zebrafish Ventral Habenula As a Homolog of the Mammalian Lateral Habenula
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DOI：
10.1523/jneurosci.3690-09.2010
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发表时间：
2010-01-27
影响因子：
5.3
通讯作者：
Okamoto, Hitoshi
中科院分区：
文献类型：
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作者：
Amo, Ryunosuke;Aizawa, Hidenori;Okamoto, Hitoshi
哺乳动物缰核由内侧缰核和外侧缰核组成。最近的行为和电生理学研究表明，外侧缰核通过影响多巴胺能和血清素能神经元的活动，在控制运动和认知行为方面发挥着关键作用。尽管具有功能意义，但由于缺乏斑马鱼等遗传上可访问的动物模型，操纵该通路中的神经活动仍然很困难。为了解决斑马鱼外侧缰核保护水平的问题，我们将束追踪技术应用于表达 GFP（绿色荧光蛋白）的转基因斑马鱼，以识别投射到中缝核的缰核神经元，中缝核是哺乳动物外侧缰核的主要目标。活鱼和固定鱼的轴突追踪显示斑马鱼腹侧缰核轴突投射到中缝的腹侧部分，但不投射到背侧缰核投射的脚间核。腹侧缰核表达原钙粘蛋白10a，这是大鼠外侧缰核的特异性标记物，而背侧缰核则没有这种表达。基因表达分析表明，成虫中位于腹内侧的腹侧缰核起源于发育过程中背侧缰核外侧的原基区域。这表明斑马鱼缰核在发育过程中出现，具有类似于哺乳动物内侧和外侧缰核的中外侧方向。这些发现表明，外侧缰核通路是进化上保守的通路，可能通过调节单胺能活性来控制脊椎动物的适应性行为。
The mammalian habenula consists of the medial and lateral habenulae. Recent behavioral and electrophysiological studies suggested that the lateral habenula plays a pivotal role in controlling motor and cognitive behaviors by influencing the activity of dopaminergic and serotonergic neurons. Despite the functional significance, manipulating neural activity in this pathway remains difficult because of the absence of a genetically accessible animal model such as zebrafish. To address the level of lateral habenula conservation in zebrafish, we applied the tract-tracing technique to GFP (green fluorescent protein)-expressing transgenic zebrafish to identify habenular neurons that project to the raphe nuclei, a major target of the mammalian lateral habenula. Axonal tracing in live and fixed fish showed projection of zebrafish ventral habenula axons to the ventral part of the median raphe, but not to the interpeduncular nucleus where the dorsal habenula projected. The ventral habenula expressed protocadherin 10a, a specific marker of the rat lateral habenula, whereas the dorsal habenula showed no such expression. Gene expression analyses revealed that the ventromedially positioned ventral habenula in the adult originated from the region of primordium lateral to the dorsal habenula during development. This suggested that zebrafish habenulae emerge during development with mediolateral orientation similar to that of the mammalian medial and lateral habenulae. These findings indicated that the lateral habenular pathways are evolutionarily conserved pathways and might control adaptive behaviors in vertebrates through the regulation of monoaminergic activities.