# Single-cell Transcriptomic Analysis of Cell Type Plasticity in Barrel Cortex of Normal and Autism Model Mice

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA BERKELEY · 2024 · $17,507

## Abstract

PROJECT SUMMARY
During postnatal developmental stages known as critical periods (CPs), sensory experience acts upon a
genetically-hardwired connectivity map to sculpt the neocortical circuitry that enables mammalian functioning.
Neurodevelopmental disorders such as autism disrupt this experience-dependent plasticity and compromise
the development of social, cognitive, and physical function. Since autism spectrum disorder (ASD) patients
suffer from tactile hyper- or hypo-sensitivity that may reflect abnormal development of sensory circuits, ASD is
commonly studied in primary somatosensory cortex (S1). In addition, the mouse whisker S1 is a somatotopic
map of the mouse whisker pad, so manipulation of specific whiskers induces observable functional changes in
the corresponding barrels of S1. Morphological and physiological studies of experience-dependent plasticity in
S1 have revealed several CPs and elucidated the influence of ASD on their emergence in mouse models of
autism. However, the gene expression programs underlying experience-dependent plasticity and the
influence of ASD on it remain unknown at the resolution of S1’s 100+ transcriptomically distinct cell
types. Since these cell types form the circuits that carry out sensory function, it is important to study the
influence of experience and ASD on their maturation. This project combines single-nucleus mRNA sequencing
(snRNA-seq) and computational biology approaches rooted in machine learning with temporally resolved
whisker manipulations and a mouse model of ASD to test two hypotheses. To test the hypothesis that whisker
experience is required for cell type development in S1, snRNA-seq will be performed at several time points
spanning two established CPs in whisker-deprived and control mice. Unsupervised and supervised machine
learning approaches such as dimensionality reduction, clustering, graph embedding, and classification will be
used to identify transcriptomic cell types at each time point and assess the influence of whisker experience on
their maturation. Hybridization chain reaction fluorescence in situ hybridization (HCR-FISH) will enable the
validation of cell type-specific development patterns. To test the hypothesis that ASD disrupts
experience-dependent cell type maturation, snRNA-seq will be performed on Fmr1 KO mice under whisker
deprivation and control conditions. Fmr1 KO models Fragile X syndrome, the most frequent monogenic cause
of intellectual disability and ASD in humans. While Fmr1 deletion has been shown to delay the maturation of
circuits in S1 during a CP, its influence on experience-dependent maturation of S1 cell types remains unknown.
Comparing gene expression profiles and cell types between KO and wild-type mice with and without
whisker-deprivation will reveal transcriptomic signatures of ASD and pinpoint the cell types in which its effects
are localized. Knowledge generated from this study about the manifestation of ASD in transcriptomic cell types
will improve...

## Key facts

- **NIH application ID:** 10912526
- **Project number:** 5F31NS131016-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Salwan Butrus
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $17,507
- **Award type:** 5
- **Project period:** 2023-09-01 → 2024-12-20

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10912526

## Citation

> US National Institutes of Health, RePORTER application 10912526, Single-cell Transcriptomic Analysis of Cell Type Plasticity in Barrel Cortex of Normal and Autism Model Mice (5F31NS131016-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10912526. Licensed CC0.

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