Siemann J K, Muller C L, Forsberg C G, Blakely R D, Veenstra-VanderWeele J, Wallace M T
Neuroscience Program, Vanderbilt University, Nashville, TN, USA.
Department of Psychiatry, Vanderbilt University, Nashville, TN, USA.
Transl Psychiatry. 2017 Mar 21;7(3):e1067. doi: 10.1038/tp.2017.17.
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.
在许多自闭症谱系障碍(ASD)儿童中都观察到了感觉加工的改变,越来越多的证据表明,这些缺陷延伸到了跨不同感官的信息整合(即多感官功能)。血清素系统在感觉发育和功能中起着重要作用,有人提出血清素信号的改变在ASD中起作用。血清素转运体(SERT)的一个功能获得性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,包括社交和沟通功能的破坏以及重复行为。当前的研究旨在测试与相同遗传背景的野生型(WT)动物相比,这些小鼠在多感官功能上是否也表现出变化。在视觉、听觉和配对视听(多感官)条件下进行测试之前,先训练小鼠分别对听觉和视觉刺激做出反应。WT小鼠在视听条件下的反应准确性有显著提高。相比之下,尽管SERT突变动物在学习听觉和视觉任务方面与WT同窝小鼠相当,但它们在多感官条件下未能表现出行为改善。我们认为,这些结果提供了首个行为证据,证明与ASD相关的基因小鼠模型存在多感官缺陷,并表明血清素系统在多感官加工以及ASD中出现的多感官变化中起作用。