Mechanisms of alcohol influence on fear conditioning: a computational model

Abstract

AbstractA connection between stress-related illnesses and alcohol use disorders is extensively documented. Fear conditioning is a standard procedure used to study stress learning and links it to the activation of amygdala circuitry. However, the connection between the changes in amygdala circuit and function induced by alcohol and fear conditioning is not well established. We introduce a computational model to test the mechanistic relationship between amygdala functional and circuit adaptations during fear conditioning and the impact of acute vs. repeated alcohol exposure. In accordance with experiments, both acute and prior repeated alcohol decreases speed and robustness of fear extinction in our simulations. The model predicts that, first, the delay in fear extinction in alcohol is mostly induced by greater activation of the basolateral amygdala (BLA) after fear acquisition due to alcohol-induced modulation of synaptic weights. Second, both acute and prior repeated alcohol shifts the amygdala network away from the robust extinction regime by inhibiting the activity in the central amygdala (CeA). Third, our model predicts that fear memories formed in acute or after chronic alcohol are more connected to the context. Thus, the model suggests how circuit changes induced by alcohol may affect fear behaviors and provides a framework for investigating the involvement of multiple neuromodulators in this neuroadaptive process.