Subcortical multisensory integration in mouse models of autism spectrum disorder

  • Awarded: 2018
  • Award Type: Pilot
  • Award #: 574347

Sensorimotor deficits are believed to contribute to many of the symptoms of autism spectrum disorder (ASD), including social impairments. For example, individuals with ASD struggle to integrate across sensory modalities. This may contribute to communication impairments, as processing speech in social contexts requires the integration of multiple sensory inputs, including assembling a coherent percept from the sound of the speaker’s voice and the sight of their lip movements and facial expressions. Consequently, understanding multisensory integration and how it is altered in ASD has the potential to yield broad insights into the circuit basis of ASD and to identify more potent therapies.

The midbrain superior colliculus (SC) is a hub for sensorimotor integration, with neurons that respond synergistically to spatially aligned multisensory stimuli and movements toward the corresponding location in space, such as the sight and sound of a person speaking. Yet surprisingly little is known about whether and how SC circuit alterations impact ASD. Evan Feinberg hypothesizes that SC deficits contribute to ASD and that investigating this structure at the circuit and behavioral levels may lead to new therapeutic interventions.

Feinberg intends to test the hypotheses that ASD mutations alter the ability of SC neurons to perform multisensory integration, causing impaired multisensory behavior. To do so, Feinberg will establish a new, multisensory head-fixed orienting task. He will then assess wild-type and ASD model mice (such as Mecp2 and Shank3 mutants) in this paradigm while monitoring SC neuronal activity using two-photon calcium imaging. These studies have the potential to reveal at the circuit and behavioral levels how multisensory stimuli are processed in health and in ASD, and may help to identify new therapeutic targets in ASD.

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