# Circuit Disruptions Underlying Atypical Sensory Processing in Fragile X Syndrome

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $476,258

## Abstract

SUMMARY
The underlying brain defects in Fragile X Syndrome (FXS) are not well understood. We have been
investigating the specific circuit alterations that lead to a variety of symptoms in FXS, including attention deficit,
anxiety, hyperarousal, sensory hypersensitivity and delayed learning. We focus on FXS, the most common
inherited cause of autism and intellectual disability, because most investigators use the same Fmr1 knockout
mouse model to investigate it, and because it lacks neuropathological features that often confound
investigations in other neurodevelopmental disorders (e.g., severe epilepsy, neuronal migration defects, etc.).
We strive to overcome limitations of previous studies by comparing the performance of humans and mice with
FXS on analogous behavioral tasks. Our goal is to identify shared deficits in sensory processing and learning
across both species that will hopefully improve outcomes of future clinical trials in FXS. Here, we will
determine the impact of sensory distractors on behavioral performance in both humans and mice using a visual
discrimination task. We will also identify specific alterations in population dynamics of pyramidal neurons and
different subtypes of inhibitory interneurons that are responsible for deficits in sensory discrimination in Fmr1
knockout mice. Building on our recently published study in Nature Neuroscience (Goel et al., 2018), we will
address the following important questions: 1. Does distraction worsen performance in a sensory discrimination
task in Fmr1 knockout mice and in adult subjects with FXS? (Aim 1)? 2. Is the firing of parvalbumin (PV)- and
vasoactive intestinal polypeptide (VIP)-expressing interneurons disrupted in Fmr1 knockout mice during the
sensory discrimination task, especially in the presence of sensory distractors? (Aim 2A)? 3. Can silencing VIP
interneurons (or exciting PV neurons) with DREADDs rescue behavioral performance in Fmr1 knockout mice?
(Aim 2B)? 4. Do mice and humans with FXS share similar deficits in neural oscillations (Aim 3)? The mouse
studies will be performed in the laboratory of established FXS investigator Carlos Portera-Cailliau (PI) at
UCLA. Craig Erickson (co-I), who runs the world’s 3rd largest FXS clinic at the University of Cincinnati, will
conduct the human studies. The experimental design exploits cutting edge in vivo imaging techniques (e.g.,
chemogenetics, in vivo two-photon calcium imaging, Cre-Lox genetics, silicon probe recordings, phase-
amplitude coupling analysis of EEG) and seeks to address important knowledge gaps in ASD pathogenesis.

## Key facts

- **NIH application ID:** 10033726
- **Project number:** 1R01NS117597-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Craig Erickson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $476,258
- **Award type:** 1
- **Project period:** 2020-07-15 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10033726

## Citation

> US National Institutes of Health, RePORTER application 10033726, Circuit Disruptions Underlying Atypical Sensory Processing in Fragile X Syndrome (1R01NS117597-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10033726. Licensed CC0.

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