Role of the infralimbic cortex in response strategy selection and habitual ethanol consumption.

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Maladaptive behaviors are characterized by the inability to update actions when goals change. These inflexible behaviors likely consist of habits in which actions are no longer performed in relation to their outcome. Extensive research has focused on elucidating the circuitry underlying habit formation and expression. Habitual behaviors are of particular interest in understanding persistent alcohol seeking that contributes to alcohol-use disorders. Indeed, alcoholics have been shown to exhibit increased reliance on habit-like response strategies as well as activation of the neurocircuitry supporting habitual behavior. While it is generally thought that prefrontal cortex subregions mediate cognitive control of actions, the infralimbic prefrontal cortex (IfL-C) appears to sub-serve habitual, stimulus-driven reward seeking. The IfL-C is critical for both the acquisition and expression of habitual behavior. Using a mouse model that enables within subjects assessment of neural activity during goal-directed and habitual behavior, we identified the emergence of response strategy-specific patterns in neural activity within the infralimbic prefrontal cortex. We observed that during goal-directed reward seeking, responses that lead to an outcome (reward delivery) were followed by an increase in firing rate in infralimbic prefrontal cortex. In contrast, during the performance of habitual reward seeking, this increase in firing rate was absent, indicating that infralimbic PFC is not encoding outcome information during the performance of outcome-insensitive behaviors. These data are the first to provide novel insight into the computational actions of infralimbic prefrontal cortex during reward seeking behavior and identify a potential neural mechanism by which the infralimbic prefrontal cortex acts to mediate the development of contingency-insensitive behaviors (i.e., alcohol habits), and further suggest that activity patterns within discrete subregions of the prefrontal cortex during precise task epochs may sub-serve the development of inflexible drinking behavior. Additional studies in our lab reveal that the development of ethanol habits involves alterations in infralimbic glutamatergic neurotranmission in the shell region of the nucleus accumbens. Specifically, we demonstrate that chronic ethanol exposure drives impairments in the ability to use reward-paired cues to adaptively regulate behavior, and further show that mGluR2/3 receptors represent a therapeutic target for restoration of these deficits in behavioral control in the alcoholic.