Specialized neurons in the right habenula mediate response to aversive olfactory cues.
Specialized neurons in the right habenula mediate response to aversive olfactory cues.
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DOI：
10.7554/elife.72345
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发表时间：
2021-12-08
期刊：
影响因子：
7.7
通讯作者：
Halpern ME
中科院分区：
文献类型：
--
作者：
Choi JH;Duboue ER;Macurak M;Chanchu JM;Halpern ME
大脑半球的特化在功能水平上得到了很好的研究，但对潜在的神经机制知之甚少。我们确定了一个小簇的胆碱能神经元在背缰（dHb）的斑马鱼，由他们的卵磷脂视黄醇酰基转移酶结构域的表达，包含2个（lratd 2a）基因和他们的传出连接与腹脚间核（vIPN）的一个亚区。右dHb中的lratd 2a表达神经元由来自左嗅球和右嗅球的二尖瓣细胞的子集支配，并且在暴露于对成年斑马鱼具有排斥性的气味尸胺时被激活。使用交叉策略来驱动肉毒杆菌神经毒素在这些神经元中的特异性表达，我们发现成年人不再对尸胺表现出厌恶。缺乏这些神经元的左异构化dHb突变体也较少受到尸胺的排斥，并且它们对警报物质（一种有效的厌恶线索）的行为反应减弱。然而，突变体，其中两个dHb有正确的身份出现更反应报警物质。结果表明，在排斥性嗅觉线索的处理和调制所产生的行为反应的不对称dHb-vIPN神经回路。
Hemispheric specializations are well studied at the functional level but less is known about the underlying neural mechanisms. We identified a small cluster of cholinergic neurons in the dorsal habenula (dHb) of zebrafish, defined by their expression of the lecithin retinol acyltransferase domain containing 2 a (lratd2a) gene and their efferent connections with a subregion of the ventral interpeduncular nucleus (vIPN). The lratd2a-expressing neurons in the right dHb are innervated by a subset of mitral cells from both the left and right olfactory bulb and are activated upon exposure to the odorant cadaverine that is repellent to adult zebrafish. Using an intersectional strategy to drive expression of the botulinum neurotoxin specifically in these neurons, we find that adults no longer show aversion to cadaverine. Mutants with left-isomerized dHb that lack these neurons are also less repelled by cadaverine and their behavioral response to alarm substance, a potent aversive cue, is diminished. However, mutants in which both dHb have right identity appear more reactive to alarm substance. The results implicate an asymmetric dHb-vIPN neural circuit in the processing of repulsive olfactory cues and in modulating the resultant behavioral response.