# Connectivity of Adult-Generated Dentate Granule Cells in a Mouse Model of Prenatal Alcohol Exposure

> **NIH NIH F31** · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · 2020 · $27,289

## Abstract

PROJECT SUMMARY/ABSTRACT
The overall goal of the proposed research is to characterize alterations in network connectivity of adult-
generated dentate granule cells (aDGCs) in a mouse model of prenatal alcohol exposure (PAE). If successful,
these studies may reveal mechanisms that underlie deficits in hippocampal function associated with fetal alcohol
spectrum disorders (FASDs). The current proposal is designed to test the overall hypothesis that PAE disrupts
experience-dependent remodeling of connectivity of newborn dentate granule neurons in the adult hippocampus.
The proposal is premised on previous work demonstrating that exposure to even moderate levels of alcohol
throughout gestation leads to an impaired neurogenic response to enriched environment and altered synaptic
activity of aDGCs as assessed electrophysiologically. I will utilize a well-characterized limited access gestational
exposure model in mice to characterize the impact of PAE on circuit connectivity of aDGCs. Specifically, I will
utilize a combination of dual-vector tracing, high-resolution confocal imaging, electrophysiological and
optogenetic approaches to address the following aims. Specific Aim 1. To test the hypothesis that PAE
disrupts EE-mediated remodeling of afferent synaptic input to aDGCs. Here we will assess the impact of
PAE on the distribution of monosynaptic afferent input to aDGCs using a dual vector tracing system (Aim 1.1),
morphological analysis of dendritic complexity and spine maturation in aDGCs (Aim 1.2), and functional synaptic
input to aDGCs using whole-cell patch slice recordings of evoked synaptic activity (Aim 1.3). Specific Aim 2.
To test the hypothesis that PAE disrupts EE-mediated remodeling of efferent synaptic output from
aDGCs. Here, I will assess the impact of PAE on excitatory efferent connections of aDGCs with CA3 pyramidal
cells and interneurons using a neuroanatomical approach (Aim 2.1), coupled with optogenetic stimulation of
aDGCs in hippocampal slice preparations (Aim 2.2). These aims coincide with the mission of the NIAAA to attain
fundamental knowledge for the improvement of alcohol-related problems, since understanding how PAE impacts
hippocampal connectivity may reveal opportunities for novel circuitry-based therapeutic approaches to mitigate
neurobehavioral consequences in clinical FASDs. Importantly, the proposed research provides a framework for
research training in alcohol-related neuroscience utilizing state-of-the art approaches within an outstanding
mentoring team and research environment within the New Mexico Alcohol Research Center.

## Key facts

- **NIH application ID:** 9983479
- **Project number:** 5F31AA027127-03
- **Recipient organization:** UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
- **Principal Investigator:** Kymberly Cheyanne Gustus
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $27,289
- **Award type:** 5
- **Project period:** 2018-08-01 → 2020-12-11

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983479

## Citation

> US National Institutes of Health, RePORTER application 9983479, Connectivity of Adult-Generated Dentate Granule Cells in a Mouse Model of Prenatal Alcohol Exposure (5F31AA027127-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9983479. Licensed CC0.

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