Alcohol-induced dysregulation of amygdala circuits and fear extinction: Integrating computational predictions with empirical evidence

Abstract

Background

Computational models suggest that both acute and chronic alcohol exposure impair fear extinction learning by destabilising amygdala circuitry, yet empirical validation has been limited.

Objective

To synthesise recent circuit manipulation studies with advanced neural network modelling and highlight their joint implications for alcohol induced dysregulation of amygdala circuits, fear extinction, and related comorbidities.

Methods

We review chemogenetic and optogenetic investigations targeting basolateral and central amygdala sub circuits, neuromodulatory systems, and stress hormone pathways, and integrate these findings with attractor network and alternative computational approaches.

Key Findings

Contemporary data corroborate model predictions that chronic intermittent ethanol heightens basolateral amygdala excitability, alters non Hebbian synaptic plasticity, and disrupts medial prefrontal cortex–amygdala communication. These changes elevate fear responses and anxiety like behaviours, mirroring post traumatic stress disorder (PTSD) and alcohol use disorder (AUD) phenotypes. Computational frameworks further explain how stress hormones and developmental timing modulate these effects, offering testable hypotheses for rodent to human translation.

Conclusions

By unifying computational and empirical advances, this commentary refines mechanistic understanding of alcohol related fear extinction deficits and underscores the clinical relevance of targeting amygdala circuits in PTSD AUD comorbidity.