# Mechanisms Governing Activity-dependent Postnatal Brain Development

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $618,790

## Abstract

PROJECT SUMMARY
 There is an urgent need to fully understand the fundamental mechanisms governing brain development
during the early postnatal period, a period that is critical in establishing the correct brain wiring for lifelong
behavioral and cognitive functions and a period during which, unsurprisingly, symptoms of many
neurodevelopmental disorders (NDDs) start to manifest. The functional maturation of the postnatal brain is highly
influenced by neuronal activity, but the mechanisms by which neuronal activity drives synaptic and circuit
maturation are poorly understood. It is particularly challenging to gain a whole brain view of the maturation
process because, in addition to the tremendous heterogeneity within the neuronal population, activity-dependent
maturation is highly variable across the brain, with different regions undergoing maturation at different times and
speeds. To meet this challenge, we have developed a genetic tool to capture the neuronal populations as they
undergo activity-dependent circuit maturation. With this tool combined with tissue clearing and whole brain
volume imaging, we propose to construct, for the first time, a spatiotemporal map of postnatal whole brain circuit
maturation. We will also examine the whole brain impact of developmental interventions, paving the way to
creating a discovery platform to study NDDs. Finally, taking advantage of our ability to distinguish neurons that
have undergone activity-dependent maturation from their less mature counterparts, we propose to uncover
molecular mechanisms underlying activity-dependent brain development. Our proposed research will provide
much-needed knowledge of postnatal brain development, and ultimately inform the design of future therapeutic
interventions to ameliorate symptoms of NDDs.

## Key facts

- **NIH application ID:** 11082910
- **Project number:** 7R01NS123710-03
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Yingxi Lin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $618,790
- **Award type:** 7
- **Project period:** 2022-05-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11082910

## Citation

> US National Institutes of Health, RePORTER application 11082910, Mechanisms Governing Activity-dependent Postnatal Brain Development (7R01NS123710-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11082910. Licensed CC0.

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