# Chronic ethanol induced disruption of goal-directed circuits

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $58,642

## Abstract

Project Summary
A significant and detrimental component of alcohol use disorder (AUD) is the disruption in decision-making
processes. Individuals with AUD show persistent deficits in decision-making processes leading to a shift to
habitual control over actions as a consequence of an impaired goal-directed system. Chronic ethanol experience
is believed to produce alterations in the neural circuits of reward and decision-making and likely contributes to
the difficulty in maintaining abstinence for individuals with AUD. However, very little is known of the specific
neural mechanisms through which ethanol dependence disrupts goal-directed decision-making. Recently, we
identified long-lasting ethanol dependence-induced projection and cell-type specific disruptions to goal-
directed decision-making circuits that result in habitual control. We found that ethanol dependence disrupted
the goal-directed circuit in which orbital frontal cortex (OFC) neurons showed a long-lasting decrease in intrinsic
excitability. Strikingly, orbitostriatal projection neurons also showed reduced transmission onto the direct, but
not indirect, output pathway of the dorsomedial striatum (DMS). Furthermore, increasing the activity of OFC
projection neurons was sufficient to restore goal-directed control in ethanol dependent mice.
Based on our recent work on CIE-induced alterations of a goal-directed circuit, we formed the central hypothesis
of this proposal: Alcohol dependence results in a bias towards habitual control over actions by disrupting goal-
directed circuits. We have evidence to show that ethanol dependence disrupts goal-directed decision-making by
attenuating neurotransmission of a known goal-directed circuit. However, attenuated OFC-DMS transmission
was measured in an ex vivo slice preparation, which begs the question, how does CIE exposure alter OFC-DMS
transmission in vivo, in awake behaving animals? Experiments in Aim 1 will focus on understanding how CIE
alters OFC-DMS plasticity in vivo and whether a change in connectivity contributes to disrupted decision-
making processes. In addition, we have shown that a change in OFC transmission can have a major influence on
decision-making processes but it is unknown how attenuated OFC-DMS transmission alters DMS output. To
address this, Aim 2 will investigate whether changes in OFC function are sufficient to alter striatal output to
modulate goal-directed actions. Elucidating the effects of ethanol dependence in vivo, specifically on OFC-DMS
transmission and DMS output, will further our understanding of the CIE-induced disruption of goal-directed
actions and the resulting habitual control.

## Key facts

- **NIH application ID:** 9972854
- **Project number:** 5F32AA026776-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Rafael Renteria
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $58,642
- **Award type:** 5
- **Project period:** 2018-06-08 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9972854

## Citation

> US National Institutes of Health, RePORTER application 9972854, Chronic ethanol induced disruption of goal-directed circuits (5F32AA026776-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9972854. Licensed CC0.

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