# Prefrontal Pathways Engaged in Excessive Alcohol Consumption

> **NIH NIH R00** · LSU HEALTH SCIENCES CENTER · 2020 · $249,000

## Abstract

PROJECT SUMMARY
Excessive alcohol consumption has widespread personal and societal consequences, negatively affecting
individual health while creating a significant economic and legal burden. Despite increasing efforts over the last
few decades to identify genetic influences and neuroadaptations that are associated with the development of
alcohol use disorders (AUDs), progress has been limited by the complexity of the underlying neuroanatomy. It
is clear that the experimental resolution needs to be improved to the level of identifying adaptations in specific
neural circuits that underlie dissociable behaviors related to AUD pathology. Thus, the goal of my research is
to identify the neuroadaptations resulting from adolescent binge drinking that perpetuate heavy drinking and
cognitive deficits in adulthood. I have focused my research on the prefrontal cortex (PFC), as this region
continues to develop during adolescence and may be vulnerable to heavy alcohol consumption. For instance,
PFC dysfunction is observed in binge drinkers and likely contributes to compulsive alcohol drinking and
cognitive deficits observed in AUDs. In mice, I have found that binge drinking during adolescence disrupts
performance on a PFC-dependent working memory task, increases alcohol consumption in adulthood, and
significantly alters the intrinsic excitability of PFC pyramidal neurons. Discerning the mechanisms underlying
these effects requires the use of tools capable of detecting physiological changes in specific neural circuits, as
well as the ability to modulate their activity during behavioral analyses. In the mentored phase (K99) of this
proposal, I will learn to use viral genetic strategies to visualize PFC projections affected by binge drinking and
characterize the circuit-specific changes in excitability following adolescent binge drinking using ex vivo
electrophysiology. Further, I will be trained to modulate PFC activity during behavior using chemogenetics,
toward the goal of determining the specific role of these prefrontal pathways in binge-drinking and working
memory. In the R00 phase, I will utilize a newly developed system for gaining permanent genetic access to
neuronal ensembles that are active during defined behaviors (FosTRAP). In combination with the techniques
learned in the mentored phase, I will use this technique to identify, characterize and modulate neuronal
ensembles engaged in binge-like alcohol consumption. Taken together, the experiments in this proposal were
designed to test the overarching hypothesis that adolescent binge drinking differentially affects the intrinsic
excitability of medial PFC pyramidal neuron subpopulations and that these subpopulations play separate roles
in binge alcohol consumption and working memory. The proposed experiments will integrate my previous
training in behavioral pharmacology, immunohistochemistry and electrophysiology with new viral genetic
strategies to identify and manipulate neural circuits. This traini...

## Key facts

- **NIH application ID:** 10131333
- **Project number:** 4R00AA024507-04
- **Recipient organization:** LSU HEALTH SCIENCES CENTER
- **Principal Investigator:** Michael Charles Salling
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $249,000
- **Award type:** 4N
- **Project period:** 2020-04-10 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10131333

## Citation

> US National Institutes of Health, RePORTER application 10131333, Prefrontal Pathways Engaged in Excessive Alcohol Consumption (4R00AA024507-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10131333. Licensed CC0.

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