Sensorimotor gating in larval zebrafish
Sensorimotor gating in larval zebrafish
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DOI：
10.1523/jneurosci.0615-07.2007
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发表时间：
2007-05-02
影响因子：
5.3
通讯作者：
Granato, Michael
中科院分区：
文献类型：
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作者：
Burgess, Harold A.;Granato, Michael
在感官刺激丰富的自然环境中控制行为需要忽略多余的信息。在某种程度上，这是通过选择性传输或门控信号到运动系统来实现的。感觉运动门控的定量和临床上重要的测量是惊吓反应的前脉冲抑制（PPI），其中的损伤已在包括精神分裂症在内的几种神经精神障碍中得到证实。在这里，我们第一次表明，在斑马鱼幼虫的声惊吓反应调制弱前脉冲的方式类似于哺乳动物PPI。我们证明，在哺乳动物中，抗精神病药物可以抑制多巴胺受体激动剂引起的斑马鱼PPI中断。由于PPI的遗传因素还不清楚，我们进行了筛选并分离出PPI降低的突变株系。对奥菲利亚突变体的分析表明，它们具有正常的感觉敏锐度和惊吓性能，但PPI降低，这表明奥菲利亚对感觉信息的中枢处理至关重要。因此，我们的研究结果提供了第一个证据的感觉运动门控在幼斑马鱼和报告的第一个公正的屏幕，以确定基因调节这一过程。
Control of behavior in the natural environment where sensory stimuli are abundant requires superfluous information to be ignored. In part, this is achieved through selective transmission, or gating of signals to motor systems. A quantitative and clinically important measure of sensorimotor gating is prepulse inhibition (PPI) of the startle response, impairments in which have been demonstrated in several neuropsychiatric disorders, including schizophrenia. Here, we show for the first time that the acoustic startle response in zebrafish larvae is modulated by weak prepulses in a manner similar to mammalian PPI. We demonstrate that, like in mammals, antipsychotic drugs can suppress disruptions in zebrafish PPI induced by dopamine agonists. Because genetic factors underlying PPI are not well understood, we performed a screen and isolated mutant lines with reduced PPI. Analysis of Ophelia mutants demonstrates that they have normal sensory acuity and startle performance, but reduced PPI, suggesting that Ophelia is critical for central processing of sensory information. Thus, our results provide the first evidence for sensorimotor gating in larval zebrafish and report on the first unbiased screen to identify genes regulating this process.