Dataset Information

Targeting Peripheral Somatosensory Neurons to Improve Tactile-Related Phenotypes in ASD Models.

ABSTRACT: Somatosensory over-reactivity is common among patients with autism spectrum disorders (ASDs) and is hypothesized to contribute to core ASD behaviors. However, effective treatments for sensory over-reactivity and ASDs are lacking. We found distinct somatosensory neuron pathophysiological mechanisms underlie tactile abnormalities in different ASD mouse models and contribute to some ASD-related behaviors. Developmental loss of ASD-associated genes Shank3 or Mecp2 in peripheral mechanosensory neurons leads to region-specific brain abnormalities, revealing links between developmental somatosensory over-reactivity and the genesis of aberrant behaviors. Moreover, acute treatment with a peripherally restricted GABAA receptor agonist that acts directly on mechanosensory neurons reduced tactile over-reactivity in six distinct ASD models. Chronic treatment of Mecp2 and Shank3 mutant mice improved body condition, some brain abnormalities, anxiety-like behaviors, and some social impairments but not memory impairments, motor deficits, or overgrooming. Our findings reveal a potential therapeutic strategy targeting peripheral mechanosensory neurons to treat tactile over-reactivity and select ASD-related behaviors.

SUBMITTER: Orefice LL

PROVIDER: S-EPMC6704376 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Publications

Targeting Peripheral Somatosensory Neurons to Improve Tactile-Related Phenotypes in ASD Models.

Orefice Lauren L LL Mosko Jacqueline R JR Morency Danielle T DT Wells Michael F MF Tasnim Aniqa A Mozeika Shawn M SM Ye Mengchen M Chirila Anda M AM Emanuel Alan J AJ Rankin Genelle G Fame Ryann M RM Lehtinen Maria K MK Feng Guoping G Ginty David D DD

Cell 20190801 4

Somatosensory over-reactivity is common among patients with autism spectrum disorders (ASDs) and is hypothesized to contribute to core ASD behaviors. However, effective treatments for sensory over-reactivity and ASDs are lacking. We found distinct somatosensory neuron pathophysiological mechanisms underlie tactile abnormalities in different ASD mouse models and contribute to some ASD-related behaviors. Developmental loss of ASD-associated genes Shank3 or Mecp2 in peripheral mechanosensory neuron ...[more]

PMID: 31398341

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Project description:Tactile stimuli on moving limbs are typically attenuated during reach planning and execution. This phenomenon has been related to internal forward models that predict the sensory consequences of a movement. Tactile suppression is considered to occur due to a match between the actual and predicted sensory consequences of a movement, which might free capacities to process novel or task-relevant sensory signals. Here, we examined whether and how tactile suppression depends on the relevance of somatosensory information for reaching. Participants reached with their left or right index finger to the unseen index finger of their other hand (body target) or an unseen pad on a screen (external target). In the body target condition, somatosensory signals from the static hand were available for localizing the reach target. Vibrotactile stimuli were presented on the moving index finger before or during reaching or in a separate no-movement baseline block, and participants indicated whether they detected a stimulus. As expected, detection thresholds before or during reaching were higher compared with baseline. Tactile suppression was also stronger for reaches to body targets than external targets, as reflected by higher detection thresholds and lower precision of detectability. Moreover, detection thresholds were higher when reaching with the left than with the right hand. Our results suggest that tactile suppression is modulated by position signals from the target limb that are required to reach successfully to the own body. Moreover, limb dominance seems to affect tactile suppression, presumably due to disparate uncertainty of feedback signals from the moving limb.NEW & NOTEWORTHY Tactile suppression on a moving limb has been suggested to release computational resources for processing other relevant sensory events. In the current study, we show that tactile sensitivity on the moving limb decreases more when reaching to body targets than external targets. This indicates that tactile perception can be modulated by allocating processing capacities to movement-relevant somatosensory information at the target location. Our results contribute to understanding tactile processing and predictive mechanisms in the brain.

Dataset Information

Targeting Peripheral Somatosensory Neurons to Improve Tactile-Related Phenotypes in ASD Models.

Publications

Targeting Peripheral Somatosensory Neurons to Improve Tactile-Related Phenotypes in ASD Models.

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