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An autism-associated serotonin transporter variant disrupts multisensory processing

机译:自闭症相关的5-羟色胺转运蛋白变异体破坏了多感觉过程

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摘要

Altered sensory processing is observed in many children with autism spectrum disorder (ASD), with growing evidence that these impairments extend to the integration of information across the different senses (that is, multisensory function). The serotonin system has an important role in sensory development and function, and alterations of serotonergic signaling have been suggested to have a role in ASD. A gain-of-function coding variant in the serotonin transporter (SERT) associates with sensory aversion in humans, and when expressed in mice produces traits associated with ASD, including disruptions in social and communicative function and repetitive behaviors. The current study set out to test whether these mice also exhibit changes in multisensory function when compared with wild-type (WT) animals on the same genetic background. Mice were trained to respond to auditory and visual stimuli independently before being tested under visual, auditory and paired audiovisual (multisensory) conditions. WT mice exhibited significant gains in response accuracy under audiovisual conditions. In contrast, although the SERT mutant animals learned the auditory and visual tasks comparably to WT littermates, they failed to show behavioral gains under multisensory conditions. We believe these results provide the first behavioral evidence of multisensory deficits in a genetic mouse model related to ASD and implicate the serotonin system in multisensory processing and in the multisensory changes seen in ASD.
机译:在许多患有自闭症谱系障碍(ASD)的儿童中,感觉过程发生了变化,越来越多的证据表明,这些障碍扩展到了跨不同感官的信息整合(即多感觉功能)。血清素系统在感觉发育和功能中起重要作用,血清素能信号的改变已被认为在ASD中起作用。血清素转运蛋白(SERT)中的功能获得编码变体与人类的感觉厌恶有关,当在小鼠中表达时,会产生与ASD相关的特征,包括社交和交流功能的破坏以及重复性行为。当前的研究旨在测试与相同遗传背景下的野生型(WT)动物相比,这些小鼠是否还表现出多感官功能的变化。在视觉,听觉和配对视听(多感官)条件下对小鼠进行测试之前,对小鼠进行了独立于听觉和视觉刺激的训练。 WT小鼠在视听条件下显示出明显的响应准确度提高。相比之下,尽管SERT突变动物在听觉和视觉任务上与WT同窝仔相当,但它们未能在多感官条件下表现出行为上的收获。我们相信这些结果提供了与ASD相关的遗传小鼠模型中多感官缺陷的第一个行为证据,并暗示5-羟色胺系统参与了多感官加工以及在ASD中出现的多感官变化。

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