# 8/8: INIA Stress and Chronic Alcohol Interactions: Cross-species plasticity signatures of alcohol and stress

> **NIH NIH U01** · VANDERBILT UNIVERSITY · 2024 · $399,110

## Abstract

Project Summary
Preexisting cognitive deficits or exposure to stressors both increase the probability of alcohol use disorder (AUD).
These relationships are bidirectional, and excessive alcohol consumption can also directly impact cognition and
dysregulate stress systems. Individual differences in cognition and stress reactivity are thought to define
phenotypes within the AUD spectrum which may differ in disease prognosis and responsivity across treatment
strategies. As such, precisely defining the behavioral and neurobiological substrates mediating covariance
across cognitive, stress, and drinking domains is critical for our understanding of AUD. However, until recently
we have lacked technical approaches which would allow for determination of whether individual differences in
these behaviors arise from the same neurons or from distinct populations within brain regions. To parse how
these phenotypes manifest we must 1) quantify the complex individual differences that emerge at the intersection
of stress, alcohol drinking, and cognitive function and 2) determine the precise neurons in the brain that control
these interactions. To this end, we will first use deep phenotyping of both behavioral and neuronal features to
computationally define individual differences across domains in mice. Previous studies have demonstrated that
prefrontal cortex is a critical mediator of cognitive function, responses to stressors, and drinking, but the precise
degree of shared circuitry between these behaviors is unclear. Thus, we will use a longitudinal design to define
the neuronal plasticity signatures in prefrontal cortex that govern expression and interactions between these
behaviors within the same subjects. Mouse models offer unique advantages for defining the precise cell-types
within the prefrontal cortex that give rise to these behaviors, but it will also be essential to determine if these
neurobehavioral relationships are conserved in higher-order species. Using a cross-species approach,
conservation of relationships between plasticity in specific cortical cell-types and individual differences in
cognitive, stress, and alcohol interactions observed in mice will then be directly tested in ex vivo brain slices from
non-human primates. Successful completion of this proposal will provide novel insight into the circuit basis of
alcohol and stress interactions and advance these hypotheses across species towards translational endpoints.

## Key facts

- **NIH application ID:** 10773155
- **Project number:** 5U01AA029971-03
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Cody Siciliano
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $399,110
- **Award type:** 5
- **Project period:** 2022-02-10 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10773155

## Citation

> US National Institutes of Health, RePORTER application 10773155, 8/8: INIA Stress and Chronic Alcohol Interactions: Cross-species plasticity signatures of alcohol and stress (5U01AA029971-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10773155. Licensed CC0.

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