Burgess Harold A, Granato Michael
Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6058, USA.
J Neurosci. 2007 May 2;27(18):4984-94. doi: 10.1523/JNEUROSCI.0615-07.2007.
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.
在感觉刺激丰富的自然环境中，行为控制需要忽略多余信息。部分情况下，这是通过选择性传递或信号向运动系统的门控来实现的。感觉运动门控的一个定量且具有临床重要性的指标是惊吓反应的前脉冲抑制（PPI），在包括精神分裂症在内的几种神经精神疾病中已证实存在PPI损伤。在此，我们首次表明斑马鱼幼体的听觉惊吓反应以类似于哺乳动物PPI的方式受到弱前脉冲的调节。我们证明，与哺乳动物一样，抗精神病药物可以抑制多巴胺激动剂诱导的斑马鱼PPI破坏。由于PPI潜在的遗传因素尚未完全了解，我们进行了筛选并分离出PPI降低的突变系。对奥菲莉亚突变体的分析表明，它们具有正常的感觉敏锐度和惊吓表现，但PPI降低，这表明奥菲莉亚对于感觉信息的中枢处理至关重要。因此，我们的结果为斑马鱼幼体的感觉运动门控提供了首个证据，并报告了首个用于鉴定调节该过程基因的无偏差筛选。
