Understanding somatosensation deficits in autism spectrum disorder

  • Awarded: 2017
  • Award Type: Research
  • Award #: 515040

The majority of autism spectrum disorder (ASD) research has focused on brain-specific mechanisms and circuits, with relatively little attention to the contributions of the peripheral nervous system and spinal cord to ASD phenotypes. In particular, although abnormalities in touch perception are very common in ASD, the underlying neural mechanisms are not known.

The laboratory of David Ginty recently used mouse ASD genetic models combined with behavioral testing, synaptic analyses and electrophysiology to define both the etiology of aberrant tactile sensitivity in mouse models of ASD and the contribution of somatosensory dysfunction to the expression of ASD-like traits1. These findings showed that somatosensory neuron dysfunction underlies aberrant tactile perception in mice harboring mutations in Mecp2 and Gabrb3, and this somatosensory tactile processing deficiency during development contributes to anxiety-like behavior and social interaction deficits in adulthood.

Ginty’s laboratory has now generated new preliminary data suggesting that Shank3 mutant mice also exhibit peripheral mechanosensory neuron dysfunction. Further, acute administration of a peripherally restricted GABAA receptor agonist can improve tactile sensitivity in Mecp2, Shank3 and Fmr1 mutant mice.

Ginty’s group now proposes to understand how the peripheral somatosensory system, spinal cord and brain processing of somatosensory information are affected in a range of ASD models and to begin to translate our findings to the human condition. The team will test whether mechanoreceptor and/or spinal cord neuron development is commonly disrupted in a wide range of mouse models of ASD (Aim 1); assess touch sensitivity and develop biomarkers for tactile sensitivity in humans with idiopathic and genetic/syndromic forms of ASD (Aim 2); and test whether a pharmacological approach using peripherally restricted GABAA receptor agonists is effective for treating tactile hypersensitivity in mouse models of ASD (Aim 3). These studies will define the role of aberrant touch sensitivity in several mouse models of ASD, aid our understanding of altered touch sensitivities in individuals with ASD and provide a necessary step toward potential therapies for these deficits.



1.Orefice L.L. et al. Cell 166, 299-313 (2016) PubMed
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