# Functional Connectivity Across Development in a Mouse Model of Rett Syndrome

> **NIH NIH F31** · WASHINGTON UNIVERSITY · 2020 · $31,438

## Abstract

PROJECT SUMMARY
Intellectual and developmental disabilities (IDDs) are a collection of disorders that are characterized by
abnormalities in individuals' developmental trajectory, but the underlying biological correlates are not always
well-understood. Functional connectivity (FC) as measured by magnetic resonance imaging (fcMRI) provides a
powerful and noninvasive tool to probe the systems-level features of IDDs and resample an individual at multiple
developmental timepoints. However, for all of the human functional neuroimaging studies of development, they
have not yet established a functional connectome across age nor its links to behavior. How FC changes across
development from infancy to adulthood, and whether FC mirrors abnormal developmental behavior trajectories
in IDDs, remain questions. Rett Syndrome (RTT) is an IDD with a known genetic cause and manifests motor and
respiratory deficits as well as certain behaviors seen in IDDs such as autism spectrum disorder. However, RTT's
complete effect on neural circuits and processes is still not well-understood, in part because the brain architecture
and connectivity have not been comprehensively evaluated at the systems level. Tracing the FC and behavioral
phenotype of RTT across development could establish a presence or lack of coupling between FC and behavior.
Use of an animal model better controls for the potentially confounding genetic and environmental heterogeneity
present in human studies. This proposal will therefore track FC across development in mice, using optical intrinsic
signal imaging measures of functional connectivity (fcOIS) to circumvent fcMRI's signal-to-noise challenges in
mice. FC networks in human infants have been previously shown to vary in their development, with somatomotor
areas showing more connectivity than association cortex in infancy. Because of this difference between
developmental extremes but the lack of data regarding the developmental progression between them, I will
longitudinally image mice at 5 developmental timepoints from P15 to early adulthood and establish a baseline
pattern of FC in neurologically typical mice using calcium imaging. To establish sensitivity to IDD-related traits, I
will characterize FC patterns in the Rett Syndrome model Mecp2lox-stop and explore inter-individual differences in
the population. Finally, to probe beyond these correlative questions, I will examine how the rescue of the Mecp2
model's gene expression in GABAergic neurons affects its FC phenotype, and I will evaluate the relationship
between the model's behavioral phenotypes after rescue and its FC measures. Ultimately, the results of this
study will shed light on the nuances of longitudinal network architecture development and the interactions
between genotype, FC, and behavior that are incompletely characterized in RTT and other IDDs.

## Key facts

- **NIH application ID:** 9972750
- **Project number:** 5F31NS110222-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Rachel M Rahn
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $31,438
- **Award type:** 5
- **Project period:** 2019-07-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9972750

## Citation

> US National Institutes of Health, RePORTER application 9972750, Functional Connectivity Across Development in a Mouse Model of Rett Syndrome (5F31NS110222-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9972750. Licensed CC0.

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