# Ethanol, chloride, calcium and growth cone dynamics in embryonic GABAergic interneurons

> **NIH NIH F31** · DARTMOUTH COLLEGE · 2020 · $45,520

## Abstract

Project Summary
 Fetal alcohol spectrum disorder (FASD) is one of the leading preventable neurodevelopmental disorders
hallmarked by varying degrees of intellectual disability that includes cognitive, behavioral, sensory, and physical
deficits. While the diagnosis and management of FASD takes place postnatally, the underlying pathoetiology is
clearly embryonic but remains incompletely understood. In mice, prenatal ethanol exposure disrupts the intricate
process of tangential migration of GABAergic cortical interneurons, and this has been postulated to contribute to
long-term excitatory/inhibitory imbalance within the cortical circuits and impairments in executive function that
lasts into adulthood. What cellular processes does ethanol affect to result in this aberrant migration? In this
proposal, I will investigate the mechanisms underlying the migration of GABAergic interneurons and how this
might be disrupted following ethanol exposure.
 My preliminary data to date suggest that the Na+-K+-2Cl- co-transporter isoform 1 (NKCC1), L-type
voltage-gated calcium channels, and cytoskeletal dynamics may be involved in the action of ethanol on the
migration of GABAergic cortical interneurons. Building on this, I propose two inter-related yet independent
specific aims. Specific Aim 1 will employ a combination of perforated patch clamp recording and real-time
imaging to test the hypothesis that ethanol interacts with NKCC1 to elevate intracellular chloride levels and
enhance GABAA receptor-induced depolarization in embryonic GABAergic interneurons. Specific Aim 2 will use
fluorescence calcium and actin-microtubule imaging to test the hypothesis that ethanol alters L-type calcium
channel-dependent actin-microtubule dynamics to alter tangential migration of embryonic GABAergic cortical
interneurons.
 Overall, through this F31 proposal, I seek intellectual, conceptual, and technical training that will be
foundational for me to continue conducting research in the field of FASD, focusing on the cellular and subcellular
mechanisms underlying ethanol’s effect on neuronal migration during brain development. The proposed work
will set the groundwork for future investigations on how ethanol affects the subcellular signaling mechanisms
that mobilize the growth cone as part of the migration process, and contribute critical mechanistic insights into
how ethanol affects tangential migration and inform the design of therapeutic strategies to prevent or manage
FASD.

## Key facts

- **NIH application ID:** 9982669
- **Project number:** 5F31AA027694-02
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Stephanie Minyong Lee
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 5
- **Project period:** 2019-06-03 → 2021-06-02

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982669

## Citation

> US National Institutes of Health, RePORTER application 9982669, Ethanol, chloride, calcium and growth cone dynamics in embryonic GABAergic interneurons (5F31AA027694-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9982669. Licensed CC0.

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