Abstract
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.
Highlights
In an effort to better understand the relationship of the serotonin system to sensory and multisensory function and its potential relevance for autism, here we examined aspects of sensory and multisensory functions in serotonin transporter (SERT) Ala[56] mice
No significant differences between multisensory and the best unisensory conditions were observed for SERT Ala[56] mice at any of the tested stimulus durations. These analyses conducted at the single subject level reinforce the findings from the group data, with both highlighting that multisensory gain is a common feature in WT animals yet absent in SERT Ala[56] animals. This is the first study to demonstrate behavioral changes in multisensory function in a genetic mouse model associated with Autism spectrum disorder (ASD)
Concordant with what has been demonstrated in a variety of mammalian species,[19,61,62] including recently in the mouse by our group,[54] behavioral gain in sensory modalities in order to perform the respective behavioral tasks
Summary
Autism spectrum disorder (ASD) is characterized by impairments in social communication as well as the presence of restricted interests and repetitive behaviors.[1,2] In addition, sensory abnormalities are highly prevalent in ASD and are part of the diagnostic criteria.[3,4,5] These changes in response to sensory stimuli have been described in a number of individual sensory systems (for example, vision, touch, hearing), with ongoing research continuing to detail both the specific alterations and their mechanistic bases.[6,7,8,9] On the basis of the growing evidence for disturbances across multiple sensory systems, there has been an increased focus on examining the integration of information across the different sensory modalities, with a number of studies detailing impaired multisensory processing in ASD.[10,11,12,13,14,15,16,17] The relevance of these multisensory deficits for the autism phenotype is critical, given that multisensory integration has a central role in the construction of coherent perceptual representations, and has been shown to facilitate behavior and perception under a number of circumstances.[18,19,20,21]. The SERT Ala[56] model is of particular interest because it may represent a bridge connecting altered 5-HT function with changes in sensory and multisensory functions in ASD. These results suggest that abnormalities in the serotonin system SERT Ala[56] mice exhibit comparable behavioral performance to may lead to altered multisensory processing in ASD and provide WT mice when trained on visual and auditory stimuli opportunities for further mechanistic studies in rodents and For the visual task, no significant differences in accuracy
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