# Hypoxia-Induced Misdirection: Understanding Postnatal Inhibitory Interneuron Migration in Neonatal Hypoxic Injury

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $41,720

## Abstract

PROJECT SUMMARY/ABSTRACT
The development of the infant brain is a dynamic, intricate process that, when disrupted, can lead to long-term
neurological disability. In humans, new inhibitory interneurons (INs) continue to be born and migrate
extensively into specific cortical destinations late in gestation and into postnatal life. One common injury that
occurs during late gestation and early infancy, is neonatal hypoxic injury (HI). HI is commonly associated with
white matter injury, which has led to prior studies focusing on the myelinating cells of the brain –
oligodendrocytes. Considering the growing awareness that INs migrate through the white matter and the
frequency and clinical outcomes of HI, it is critical to understand the impact of hypoxia on late migrating INs.
To overcome the limited access to neonatal human brain tissue, we have developed an innovative model
system using the piglet brain. Using the piglet model, we have identified two migratory streams from the Arc
targeting distinct cortical structures. Our preliminary data suggests that these streams differentially express
genes encoding migratory-related receptors, most notably CXCR4. During hypoxic injury, CXCR4 is directly
upregulated by hypoxia inducible factors. Therefore, I propose that HI results in aberrant migration of
migratory INs in the postnatal cortex, a misdirection that is mediated through CXCR4 upregulation.
First, I will use computational approaches to identify altered signaling pathways in human HI (Aim 1). Next, I
will quantify the effect of hypoxia on interneuron migration (Aim 2). Finally, I will test the hypothesis that
CXCR4 regulates Arc interneuron migration and mediates hypoxic induced misdirection (Aim 3). Completion of
these aims will expand our knowledge of a fundamental mechanism in neonatal brain development and the
effect of a common injury on this process.
My primary sponsor, Dr. Mercedes Paredes, is an academic neurologist who is an expert in human inhibitory
interneuron development and my co-sponsor, Dr. John Rubenstein, discovered the role of CXCR4 in inhibitory
interneuron migration and other fundamental transcription factors regulating brain development. Together, their
experience and commitment to my training will ensure that I learn to pursue a biomedically focused scientific
question, complete the proposed research, and gain relevant clinical experiences to advance my long-term
career goals. An F31 NRSA fellowship would allow me to deepen my expertise in developmental neuroscience
and computational genomics. This training will provide a foundation to take the next steps towards becoming
an academic pediatric neurologist who studies the intersection of genetics and neurodevelopment to advance
neuroprotective and regenerative therapies for brain disorders.

## Key facts

- **NIH application ID:** 10997031
- **Project number:** 1F31NS139663-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Aunoy Poddar
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $41,720
- **Award type:** 1
- **Project period:** 2024-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10997031

## Citation

> US National Institutes of Health, RePORTER application 10997031, Hypoxia-Induced Misdirection: Understanding Postnatal Inhibitory Interneuron Migration in Neonatal Hypoxic Injury (1F31NS139663-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10997031. Licensed CC0.

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