# Role of perineuronal nets in adolescent alcohol-induced deficits

> **NIH NIH R21** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $223,531

## Abstract

Project summary/Abstract
Adolescence is a developmental period marked by risk-taking behavior and exploration, and
over 60% of 12th-graders in the US reported trying alcohol. In fact, 16% of 12th graders reported
binge drinking, or consuming 5+ drinking in a session. While human studies show that
adolescent binge drinking impacts cognitive performance and neural signals via MRI, it is
difficult to tease apart antecedent factors that may lead to binge drinking from the
consequences of the resulting alcohol exposure on the developing brain. We and others have
used animal models to show that binge-levels of alcohol exposure is sufficient to reduce
cognitive and behavioral flexibility in conditioning tasks. Moreover, these behavioral changes
are associated with a variety of neurochemical, physiological, molecular and epigenetic changes
in the brain. We have reported that adolescent intermittent ethanol (AIE) exposure resulted
deficient reversal learning, in that rats perseverated on a previously reinforced choice instead of
shifting to a different choice. We also found that AIE-exposed rats exhibited reduced functional
connectivity, measured with resting-state fMRI, among regions of interest that underlie
behavioral choice. Finally, we and others have reported AIE-induced increases in perineuronal
nets (PNNs, extracellular matrix structures that encapsulate parvalbumin (PV)-expressing
interneurons) in frontal regions such as the orbitofrontal cortex. This is important as PV+
interneurons contribute to gamma oscillations that would be reflected in functional connectivity
measures. However, it is unknown whether AIE-induced increases in PNNs contribute to the
AIE-induced behavioral and functional connectivity deficits. This project addresses that
knowledge gap by enzymatically degrading PNNs in the OFC of AIE-exposed rats and
measuring subsequent effects on reversal learning and functional connectivity MRI. To our
knowledge, the resulting data will be the first to link PNN integrity in the OFC to behavioral
flexibility and functional connectivity. These data will contribute to our understanding of the
mechanisms by which AIE persistently disrupts behavior and brain circuit function and lay the
foundation for strategies to ameliorate these effects.

## Key facts

- **NIH application ID:** 10904368
- **Project number:** 1R21AA031415-01A1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Donita L. Robinson
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $223,531
- **Award type:** 1
- **Project period:** 2024-04-17 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10904368

## Citation

> US National Institutes of Health, RePORTER application 10904368, Role of perineuronal nets in adolescent alcohol-induced deficits (1R21AA031415-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10904368. Licensed CC0.

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