# Circuit Defects Underlying Deficits in Social Touch in Fragile X Syndrome

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $426,841

## Abstract

ABSTRACT
Sensory hypersensitivity and the resulting avoidance behaviors represent a major challenge for most individuals
with Fragile X syndrome (FXS) and for many autistic people. Differences in sensory processing can also
contribute to inattention/distraction, learning disability, repetitive behaviors, and even social avoidance. Indeed,
exaggerated responses to tactile stimuli could also worsen anxiety about social interactions, especially if they
involve physical contact (e.g., shaking hands, hugging, kissing) and if the contact is unwanted. For this proposal
we will explore this relationship between sensory hypersensitivity and social experience in FXS/autism. Social
touch per se has not been investigated in animal models of autism, including FXS; therefore, it is presently
unknown whether they display unique avoidance behaviors or aversive facial expressions to different types of
social touch. It is also not known how such maladaptive behaviors to social touch might be represented in neural
dynamics of relevant brain areas. To address these knowledge gaps, we have developed a novel assay for
social touch in mice. We previously demonstrated that Fmr1-/- mice, the main model of FXS, show avoidance
and defensive behaviors to repetitive whisker stimulation, akin to tactile defensiveness in humans with FXS. In
more recent studies we have shown that Fmr1-/- mice and maternal immune activation (MIA) model mice both
show strikingly similar behavioral phenotypes in response to repeated bouts of social touch, including
hyperarousal, running avoidance, and sustained eye closure. Here, we will follow a symptom-to-circuit strategy
to better understand social touch deficits in FXS/autism. First, we will characterize behavioral responses to social
touch in Fmr1-/- and MIA mice with our novel behavioral assay we have developed. Second, we will `reverse-
engineer' such phenotypes by identifying the underlying circuit and neuronal changes using in vivo
electrophysiological recordings with Neuropixels probes. Finally, we will intervene at the level of neuronal activity
in the relevant circuits (focusing on somatosensory cortex and amygdala) with pharmacology and
chemogenetics, to mitigate deficits in social touch. Our hope is that these preclinical studies will yield significant
insights for the treatment of FXS/autism.

## Key facts

- **NIH application ID:** 10978150
- **Project number:** 2R01HD054453-16A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Carlos Portera-Cailliau
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $426,841
- **Award type:** 2
- **Project period:** 2024-08-01 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10978150

## Citation

> US National Institutes of Health, RePORTER application 10978150, Circuit Defects Underlying Deficits in Social Touch in Fragile X Syndrome (2R01HD054453-16A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10978150. Licensed CC0.

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