Department of Embryology, Carnegie Institution for Science Baltimore, MD, USA.
Front Neural Circuits. 2013 May 21;7:98. doi: 10.3389/fncir.2013.00098. eCollection 2013.
The dorsal habenular nuclei of the zebrafish epithalamus have become a valuable model for studying the development of left-right (L-R) asymmetry and its function in the vertebrate brain. The bilaterally paired dorsal habenulae exhibit striking differences in size, neuroanatomical organization, and molecular properties. They also display differences in their efferent connections with the interpeduncular nucleus (IPN) and in their afferent input, with a subset of mitral cells distributed on both sides of the olfactory bulb innervating only the right habenula. Previous studies have implicated the dorsal habenulae in modulating fear/anxiety responses in juvenile and adult zebrafish. It has been suggested that the asymmetric olfactory-habenula pathway (OB-Ha), revealed by selective labeling from an lhx2a:YFP transgene, mediates fear behaviors elicited by alarm pheromone. Here we show that expression of the fam84b gene demarcates a unique region of the right habenula that is the site of innervation by lhx2a:YFP-labeled olfactory axons. Upon ablation of the parapineal, which normally promotes left habenular identity; the fam84b domain is present in both dorsal habenulae and lhx2a:YFP-labeled olfactory bulb neurons form synapses on the left and the right side. To explore the relevance of the asymmetric olfactory projection and how it might influence habenular function, we tested activation of this pathway using odorants known to evoke behaviors. We find that alarm substance or other aversive odors, and attractive cues, activate fos expression in subsets of cells in the olfactory bulb but not in the lhx2a:YFP expressing population. Moreover, neither alarm pheromone nor chondroitin sulfate elicited fos activation in the dorsal habenulae. The results indicate that L-R asymmetry of the epithalamus sets the directionality of olfactory innervation, however, the lhx2a:YFP OB-Ha pathway does not appear to mediate fear responses to aversive odorants.
斑马鱼端脑背侧缰核已成为研究左右（L-R）不对称发育及其在脊椎动物大脑中功能的重要模型。双侧成对的背侧缰核在大小、神经解剖组织和分子特性上表现出显著差异。它们在与脚间核（IPN）的传出连接以及传入输入方面也存在差异，一小部分嗅球双侧分布的米勒细胞仅支配右侧缰核。先前的研究表明，背侧缰核参与调节幼年和成年斑马鱼的恐惧/焦虑反应。有人认为，通过 lhx2a:YFP 转基因选择性标记揭示的不对称嗅觉-缰核通路（OB-Ha）介导了警报信息素引起的恐惧行为。在这里，我们表明 fam84b 基因的表达标志着右侧缰核的一个独特区域，该区域是 lhx2a:YFP 标记的嗅球轴突支配的部位。在对通常促进左侧缰核身份的副松果体进行消融后，fam84b 区域存在于双侧背侧缰核中，并且 lhx2a:YFP 标记的嗅球神经元在左侧和右侧形成突触。为了探索不对称嗅觉投射的相关性及其如何影响缰核功能，我们使用已知引发行为的气味剂测试了该通路的激活。我们发现，警报物质或其他厌恶气味以及有吸引力的线索会激活嗅球中某些细胞中的 fos 表达，但不会激活 lhx2a:YFP 表达群体。此外，警报信息素或软骨素硫酸盐均不会引起背侧缰核 fos 的激活。结果表明，端脑的左右不对称性确定了嗅觉传入的方向性，然而，lhx2a:YFP OB-Ha 通路似乎不会介导对厌恶气味的恐惧反应。
