# Prenatal Ethanol Exposure on Executive Function

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2020 · $358,875

## Abstract

Prenatal ethanol exposure (PE) leads to fetal alcohol spectrum disorders (FASD), which consist of
many behavioral/cognitive dysfunctions including learning disabilities, behavioral disorders, and impaired
executive function. FASD is the most preventable neurodevelopmental disorder, yet the prevalence is
persistently high (2-5%) in the US. Developing effective interventions is an important goal for FASD.
 Impaired executive function is reported in 49-94% of individuals with FASD and could be the most
common cognitive deficit in FASD. However, the underlying neuronal mechanisms are not well understood.
This prevents the development of effective interventions. The medial prefrontal cortex (mPFC) is a critical
brain area controlling executive function. Understanding how PE alters the function of mPFC is key to
elucidating the underlying neuronal mechanisms of impaired executive function in FASD. Using a rat model
of FASD, we have successfully shown PE indeed leads to a persistent impairment in sustained attention, a
major component of executive function. We also find PE results in abnormal excitatory synaptic functions
including abnormal AMPA and NMDA receptor development and increased excitatory synaptic strength in
mPFC layer V pyramidal neurons (L 5 neurons). These neurons are mPFC output neurons and their role is
to integrate inputs from many brain regions and exert top down control over downstream brain regions to
regulate executive function.
 Based on the preliminary data, we hypothesize that PE-induced abnormal excitatory synaptic function
in mPFC L 5 neurons contribute to attention deficit. To test this hypothesis, we will first characterize in
detail the effects of PE on excitatory synaptic function in mPFC layer V pyramidal neurons and the
attention deficit. We will also investigate how PE effects could be influenced by different levels of ethanol
exposure and sex. We will then verify the causal relationship between PE-induced abnormality in mPFC
neurons and attention deficit. Lastly, we will investigate if postnatal environmental intervention can
promote the normalization of excitatory synapses in mPFC and rescue attention deficit in PE rats.
 The results of these studies will enhance our understanding of the neuronal mechanisms underlying
executive function deficit in FASD. They will also unravel potential mechanisms by which postnatal
environmental intervention can restore mPFC function and attention. These studies will have an important
translational impact and could help the development of new intervention strategies to treat deficits in
executive function in FASD.

## Key facts

- **NIH application ID:** 9902268
- **Project number:** 5R01AA026421-03
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** ROH-YU SHEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $358,875
- **Award type:** 5
- **Project period:** 2018-06-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9902268

## Citation

> US National Institutes of Health, RePORTER application 9902268, Prenatal Ethanol Exposure on Executive Function (5R01AA026421-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9902268. Licensed CC0.

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