An autism-associated serotonin transporter variant disrupts multisensory processing.
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.
Neuroscience Program, Vanderbilt University, Nashville, TN, USA.
J K
JK
Siemann
Neuroscience Program, Vanderbilt University, Nashville, TN, USA.
C L
CL
Muller
Department of Psychiatry, Vanderbilt University, Nashville, TN, USA.
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CG
Forsberg
Department of Psychiatry, Vanderbilt University, Nashville, TN, USA.|Silvio O. Conte Center for Neuroscience Research, Vanderbilt University, Nashville, TN, USA.|Department of Biomedical Science, Charles E. Schmidt College of Medicine, Jupiter, FL, USA.|Florida Atlantic University Brain Institute, Florida Atlantic University, Jupiter, FL, USA.|Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.
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RD
Blakely
Silvio O. Conte Center for Neuroscience Research, Vanderbilt University, Nashville, TN, USA.|Department of Psychiatry, Sackler Institute for Developmental Psychobiology, Columbia University, New York, NY, USA.|Center for Autism and The Developing Brain, New York Presbyterian Hospital, New York, NY, USA.|New York State Psychiatric Institute, New York, NY, USA.
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J
Veenstra-VanderWeele
Department of Psychiatry, Vanderbilt University, Nashville, TN, USA.|Silvio O. Conte Center for Neuroscience Research, Vanderbilt University, Nashville, TN, USA.|Department of Psychology, Vanderbilt University, Nashville, TN, USA.|Department of Hearing and Speech Sciences, Vanderbilt University, Nashville, TN, USA.|Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, TN, USA.
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MT
Wallace
D000161:Acoustic Stimulation; D000818:Animals; D001307:Auditory Perception / Q000235:genetics*; D000067877:Autism Spectrum Disorder / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D001321:Autistic Disorder / Q000235:genetics / Q000503:physiopathology / Q000523:psychology; D001522:Behavior, Animal; D003071:Cognition; D014644:Genetic Variation; D007858:Learning; D051379:Mice; D009154:Mutation; D010775:Photic Stimulation; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D014796:Visual Perception / Q000235:genetics*
D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse