# Determining the acute pharmacological effects of alcohol in rodent medial prefrontal cortex

> **NIH NIH R21** · INDIANA UNIVERSITY INDIANAPOLIS · 2021 · $213,902

## Abstract

Project Summary:
A wealth of data exists describing how alcohol influences neuronal function in brain regions necessary for
complex cognitive functions such prefrontal cortex (PFC). These data have proven critical to form hypotheses
regarding how alcohol consumption might lead to altered behavioral states (e.g. intoxication) and the
associated negative outcomes (e.g. risky behavior, violence). However, these data have been exclusively
collected in reduced preparations, such as anesthetized animals or ex vivo slice preparations, and therefore
may not adequately model how neural function is impaired by alcohol consumption in behaving subjects.
Published and preliminary data from our group indicate that the broad reductions in neural firing previously
observed in reduced preparations are not observed in awake behaving animals. This calls into question current
explanations of how alcohol affects neural function, indicating that there is a critical need for additional
experiments that demonstrate specifically how alcohol consumption affects neural function in the PFC of
awake behaving animals. The long-term goal of this work is to create a unified model of how alcohol
consumption alters the computational properties of PFC and leads to impaired behavioral control. Towards this
goal, a series of experiments are proposed in rat models to test the overarching hypothesis that alcohol
consumption leads to reductions in functional connectivity in PFC networks. In Specific Aim 1, a series
of in vivo approaches will determine how oral consumption of alcohol influences neural activity in medial PFC
(mPFC) networks. A combination of microdialysis, large-scale neural recordings, and optogenetics will be
performed to determine the cell type- and layer-specific effects of alcohol consumption on neural activity.
Experiments will be performed to determine which changes in neural activity evoked by oral consumption are
conserved following local application of physiologically-relevant concentrations of alcohol within mPFC.
Specific Aim 2 will determine which changes in neural activity observed in vivo are conserved ex vivo. In this
Aim we will trace the local effects of alcohol on mPFC from the single cell to the microcircuit level. Glutamate
uncaging will be combined with patch-clamp electrophysiology to assess network function and single cell
function. These approaches will synergize with those in Specific Aim 1 to determine which changes in neural
activity following alcohol consumption are conserved across levels of neural function and in each preparation.
Collectively, these data will facilitate future studies that will integrate how the influence of consumed alcohol on
cellular function translates into altered network properties and, ultimately, impaired behavioral states. Future
studies will also assess changes in neural function in brain-wide networks and if/how the observations herein
are altered following extended alcohol use. In sum, this proposal seeks to cl...

## Key facts

- **NIH application ID:** 10194666
- **Project number:** 1R21AA029176-01
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Christopher Court Lapish
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $213,902
- **Award type:** 1
- **Project period:** 2021-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10194666

## Citation

> US National Institutes of Health, RePORTER application 10194666, Determining the acute pharmacological effects of alcohol in rodent medial prefrontal cortex (1R21AA029176-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10194666. Licensed CC0.

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