# Generation of specialized human cell types in the mammalian brain

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $424,875

## Abstract

ABSTRACT
Stem cell-based platforms have transformed our understanding of many nervous system disorders, such as
epilepsy. However, neurons develop in a highly complex environment of an intact brain, and functional
maturation in vitro may not accurately reflect the developmental processes occurring in vivo. To accurately
recapitulate the early developmental stages of synaptic and neuronal network dysfunction in these patients,
direct access to patient neurons in an in vivo microenvironment is indispensable. Here, we propose an
innovative approach to evaluate the in vivo development and function of neurons differentiated from human
induced pluripotent stem cells. To accomplish this goal, we will develop a stem cell transplantation strategy to
graft forebrain neurons into the developing brain. Using cell type-specific markers to fluorescently label subsets
of neurons and a series of ex vivo and in vivo assays, we will record neuronal, synaptic and circuit-level
properties of both the grafted and native-born neurons simultaneously for days to weeks. If successful, our
work will provide an entirely new platform for studying epilepsy and other human nervous system disorders,
one that would allow investigators to systematically and comprehensively evaluate how patient neurons
become fully, and correctly, integrated into the developing brain circuitry and how they function in real time
during behavior. It will also form the basis from which we can test emerging therapies on transplanted patient
neurons.

## Key facts

- **NIH application ID:** 9875158
- **Project number:** 1R21NS114728-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Robert F Hunt
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $424,875
- **Award type:** 1
- **Project period:** 2020-04-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9875158

## Citation

> US National Institutes of Health, RePORTER application 9875158, Generation of specialized human cell types in the mammalian brain (1R21NS114728-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9875158. Licensed CC0.

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