# Impact of Alcohol on Claustrum Function

> **NIH NIH F32** · UNIVERSITY OF MARYLAND BALTIMORE · 2024 · $74,284

## Abstract

Project Summary / Abstract
While cognitive impairment is a key domain of alcohol use disorder, the neurocircuit mechanisms underlying this
remain poorly understood. This project invokes the claustrum, a previously unexplored brain region in the context
of alcohol, as a potential component of the circuitry impacted by chronic alcohol exposure. Preliminary data has
revealed that chronic alcohol vapor reduces membrane capacitance and frequency of excitatory synaptic inputs,
electrophysiological signatures of profound alcohol-induced neuronal atrophy in claustrum projection neurons.
This project tests the hypothesis that alcohol-induced cognitive control impairments are mediated by
blunted activity of ACC-projecting claustrum neurons. Building on prior expertise in whole-cell
electrophysiology, this project provides training in detailed neuronal morphology imaging and analysis in aim 1
to determine the impact of chronic alcohol exposure on ACC-projecting claustrum neuron synaptic activity,
intrinsic excitability, and morphology. This aim tests the predictions that, following chronic alcohol exposure,
fluorescently labeled and biocytin-filled ACC-projecting claustrum neurons will exhibit reduced membrane
capacitance and sEPSC frequency as well as dendritic and synaptic atrophy. Further, adding new skills in operant
behavior and fiber photometry, experiments in aim 2 will determine the influence of chronic alcohol exposure on
claustrum-ACC activity during a cognitively demanding behavioral task. This aim tests the prediction that chronic
alcohol vapor exposure blunts claustrum-ACC calcium activity associated with reduced accuracy and increased
impulsivity in an attentional set-shifting task. Finally, aim 3 develops technical skills in chemogenetic circuit
manipulation and the drinking-in-the-dark behavioral paradigm to test if claustrum-ACC activity regulates
inflexible, aversion resistant drinking. This aim tests the prediction that promoting or silencing claustrum-ACC
activity will inhibit or enhance aversion-resistant drinking, respectively, as measured by consumption of alcohol
adulterated with the bitter tastant quinine. Combined, these aims establish a role for the claustrum-ACC circuit
in cognitive impairments associated with alcohol use disorder with translational and therapeutic implications. The
technical expertise obtained is bolstered with conceptual training on claustrum and alcohol in relation to cognitive
control. Exceptional training is ensured by Dr. Mathur, an expert on neurocircuit studies of alcohol-induced
inflexible behaviors, and co-sponsor Dr. Cheer, an expert on neuromodulation and reward decision making in
substance use disorder, who both have stellar training records. Seated within an institution boasting state-of-the-
art facilities and a vibrant neuroscience community, professional development is further emphasized with focused
training in mentorship, teaching, collaboration, publishing, and responsible conduct of research....

## Key facts

- **NIH application ID:** 11067131
- **Project number:** 1F32AA032136-01
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Andreas Brydenfelt Wulff
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $74,284
- **Award type:** 1
- **Project period:** 2024-09-09 → 2028-09-08

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11067131

## Citation

> US National Institutes of Health, RePORTER application 11067131, Impact of Alcohol on Claustrum Function (1F32AA032136-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11067131. Licensed CC0.

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