# Identification and modulation of insula to BNST circuit specific afferents in ethanol abstinence

> **NIH NIH F30** · VANDERBILT UNIVERSITY · 2021 · $48,273

## Abstract

PROJECT SUMMARY
Alcohol use disorder (AUD) is a major health concern affecting millions of Americans with an estimated annual
cost of well over $200 Billion. A critical component in limiting the impact of AUD is preventing relapse, a
common tribulation for alcoholics. Stress dramatically increases the likelihood of reinstatement during
protracted abstinence, and patients with AUD often have comorbid anxiety disorders. Modulation of the
endocannabinoid (eCB) system can decrease the response to stressors. The insula and BNST have emerged
as regions implicated in the withdrawal phase of AUD. Evidence suggests that the insula plays a vital role in
the negative interoceptive stimuli experienced during abstinence. The BNST, part of the extended amygdala,
integrates reward and stress in addiction. Our lab has found functional monosynaptic connections between the
insula and anxiety-responsive corticotrophin-releasing factor (CRF) cells in the BNST (BNSTCRF cells). The
inputs that control the BNST projecting insular (insulaBNST) neurons and the modulation of those inputs remain
essential unknowns. The proposed research aims to understand the regulation of the insulaBNST circuit and how
it is changed in ethanol withdrawal. To do so, we will further investigate the distribution of afferents to
insulaBNST cells (subaim 1.1), establish monosynaptic connectivity between afferent regions (subaim 1.2), and
interrogate ethanol and eCB functionality at these synapses (subaim 1.3). Subaim 2.1 will ascertain the
effects of alcohol withdrawal on ex vivo slice physiology in this circuit while subaim 2.2 will establish the
implications of alcohol withdrawal in vivo using calcium imaging via fiber photometry. We hope the findings
from these experiments will provide a better understanding of the interplay between these brain regions and
how this interaction is regulated. In so doing, we will be able to establish the normal physiology and impact that
alcohol withdrawal has on this novel circuit.

## Key facts

- **NIH application ID:** 10196888
- **Project number:** 5F30AA027126-03
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Joseph Richard Luchsinger
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $48,273
- **Award type:** 5
- **Project period:** 2019-07-01 → 2022-05-13

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10196888

## Citation

> US National Institutes of Health, RePORTER application 10196888, Identification and modulation of insula to BNST circuit specific afferents in ethanol abstinence (5F30AA027126-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10196888. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*