Plasticity of Dopaminergic Phenotype and Locomotion in Larval Zebrafish Induced by Brain Excitability Changes during the Embryonic Period
Plasticity of Dopaminergic Phenotype and Locomotion in Larval Zebrafish Induced by Brain Excitability Changes during the Embryonic Period
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DOI：
10.1523/eneuro.0320-21.2023
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发表时间：
2023-06-01
期刊：
影响因子：
3.4
通讯作者：
Demarque, Michael
中科院分区：
文献类型：
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作者：
Bataille, Sandrine;Jalaber, Hadrien;Demarque, Michael
在胚胎期，神经元通讯在突触建立之前就开始了，具有替代形式的神经元兴奋性，这里称为胚胎神经兴奋性（ENE）。 ENE 已被证明可以调节发育转录程序的展开，但对发育中的生物体的整体影响尚不完全清楚。在这里，我们监测斑马鱼胚胎端脑中的钙 (Ca2+) 瞬态作为 ENE 的代表，以评估瞬态药物治疗增加或减少 ENE 的功效。胚胎期末期 ENE 的增加或减少分别促进多巴胺 (DA) 神经元数量的增加或减少。这种多巴胺能规范的可塑性发生在受精后 6 d (dpf) 的斑马鱼幼虫的大脑皮层 (SP) 中，位于相对稳定的 vMAT2 阳性细胞群内。因此，非多巴胺能 vMAT2 阳性细胞构成了可被 ENE 招募的 DA 神经元储备池的意外生物标记。治疗结束几天后，调节 ENE 也会影响幼虫的运动。特别是，ENE 从 2 dpf 增加到 3 dpf 促进了幼虫在 6 dpf 时的过度运动，让人想起针对注意力缺陷多动障碍 (ADHD) 报道的斑马鱼内表型。这些结果为识别可能干扰 ENE 的环境因素以及研究将 ENE 与神经递质规范联系起来的分子机制提供了一个方便的框架。
During the embryonic period, neuronal communication starts before the establishment of the synapses with alternative forms of neuronal excitability, called here embryonic neural excitability (ENE). ENE has been shown to modulate the unfolding of development transcriptional programs, but the global consequences for developing organisms are not all understood. Here, we monitored calcium (Ca2+) transients in the telencephalon of zebrafish embryos as a proxy for ENE to assess the efficacy of transient pharmacological treatments to either increase or decrease ENE. Increasing or decreasing ENE at the end of the embryonic period promoted an increase or a decrease in the numbers of dopamine (DA) neurons, respectively. This plasticity of dopaminergic specification occurs in the subpallium (SP) of zebrafish larvae at 6 d postfertilization (dpf), within a relatively stable population of vMAT2-positive cells. Nondopaminergic vMAT2-positive cells hence constitute an unanticipated biological marker for a reserve pool of DA neurons that can be recruited by ENE. Modulating ENE also affected larval locomotion several days after the end of the treatments. In particular, the increase of ENE from 2 to 3 dpf promoted hyperlocomotion of larvae at 6 dpf, reminiscent of zebrafish endophenotypes reported for attention deficit hyperactivity disorders (ADHDs). These results provide a convenient framework for identifying environmental factors that could disturb ENE as well as to study the molecular mechanisms linking ENE to neurotransmitter specification.