Mechanisms of behavioral inhibition: the neurophysiology of neuronal ensembles related to ethanol addiction

Abstract

One behavior to be effective depends on the choice and execution of a motor program simultaneous to opposing and unwanted actions inhibition. The ability to suppress a response varies among individuals. Accordingly, lower efficiency in the inhibition can lead to risky decision-making phenotypes and impulsive-compulsive disorders. Impulsivity is strongly related to psychoactive substance use disorder, such as alcohol abuse. A group of subcortical regions, the Basal Ganglia, are responsible for decision-making and inhibitory control in humans, primates, and rodents. The Nucleus Accumbens (NAc) is part of this set of structures and plays a role in behavioral inhibition, motivated behavior modulation, and the coding of rewards. Still, there is evidence that NAc modulates drug-seeking behaviors and reestablishment of drug consumption during abstinence. Yet, the role of NAc in this inhibition deficit is variable and dependent upon specific projections, the subregion (whether core or shell), and the neuronal ensembles analyzed. NAc receives afferents from the insular cortex, which plays a role in the formation of preference and expectation of reinforcement, and is also one of the regions responsible for the compulsive consumption of ethanol. However, little information is available about the organization and functionality of these projections. Therefore, the first objective of this study is to dissect the architecture of the insular cortex projection to NAc in mice, using anterograde and retrograde fluorescent tracers (experiment 1). In addition, we will investigate the neuronal activity of these specific pathways by patch-clamp in baseline and under the acute effect of ethanol (experiment 2). Finally, we will evaluate the electrophysiology of neuronal ensembles related to compulsive ethanol consumption in the insula and NAc by using cfos-Cre transgenic mice (experiment 3). This study will contribute to a better understanding of behavioral inhibition in normal and pathological conditions, as in deficits caused by chronic exposure to alcohol and other obsessive-compulsive disorders. (AU)