# The effects of somatosensory experience on brain development and function in autism spectrum disorders

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $373,370

## Abstract

Project Summary: Autism spectrum disorders (ASD) are a highly prevalent class of neurodevelopmental
disorders characterized by impairments in social communication and interactions, as well as restricted,
repetitive behaviors. While ASDs are heterogeneous in etiology and severity, the majority of individuals with
ASD exhibit altered sensitivity to light touch. Most ASD research has focused on brain-specific mechanisms
and circuits, with little attention to the contributions of the peripheral nervous system and spinal cord to ASD
phenotypes. We recently found that a range of ASD mouse models (Gabrb3, Mecp2 or Shank3 mutations)
exhibit over-reactivity to light touch, and this hypersensitivity is due to abnormal peripheral somatosensory
neuron function. Somatosensory abnormalities resulting from peripheral sensory neuron dysfunction during
development also lead to disruptions in primary somatosensory cortex (S1) function, as well as social
interaction deficits in adult mice (Orefice et al., Cell, 2016; Orefice et al., Cell, 2019).
 Our findings reveal peripheral somatosensory neurons as a key locus of dysfunction underlying tactile
over-reactivity in ASD, and a role for peripheral sensory neuron dysfunction in abnormal brain development
and aberrant social behaviors in ASD models. Yet, the mechanisms by which peripheral somatosensory
neuron dysfunction alters brain circuit development and results in social impairments remain
unknown. We hypothesize that ASD-related genetic mutations disrupt peripheral sensory neuron function and
tactile processing at the earliest stages of sensory pathways, leading to abnormal brain development, which
results in impaired brain function and disrupted behaviors in ASD. We propose that peripheral sensory neuron
dysfunction leads to elevated sensory inputs to the central nervous system that leads to abnormal S1 function
and altered long-range connectivity between S1 and brain regions that modulate social behaviors, including
prefrontal cortex (PFC), which ultimately impacts social interactions.
 In this proposal, we aim to understand the mechanisms through which peripheral sensory neuron
dysfunction contributes to changes in brain-driven social behaviors. Using mouse genetics, behavioral,
histological, viral, sequencing, optogenetics, and fiber photometry techniques, as well as in vitro and in vivo
electrophysiological approaches, we will: 1) characterize the microcircuit development and long-range
connectivity of trunk primary somatosensory cortex (S1TR); 2) determine whether peripheral sensory neuron
dysfunction in ASD models impacts sensory representation in S1TR; and 3) identify whether peripheral
somatosensory neuron dysfunction impacts the development of S1TR-PFC projections in ASD models.
Because of the accessibility of the peripheral nervous system, insights gleaned from our proposed studies may
lead to opportunities for therapeutic approaches for the treatment of hypersensitivity or aversion to social
touch, as ...

## Key facts

- **NIH application ID:** 10273686
- **Project number:** 1R01NS122788-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Lauren Lynn Orefice
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $373,370
- **Award type:** 1
- **Project period:** 2021-07-15 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10273686

## Citation

> US National Institutes of Health, RePORTER application 10273686, The effects of somatosensory experience on brain development and function in autism spectrum disorders (1R01NS122788-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10273686. Licensed CC0.

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