Chronic Stress Alters Striosome-Circuit Dynamics, Leading to Aberrant Decision-Making

Abstract

Effective evaluation of costs and benefits is a core survival capacity that in humans is considered as optimal, "rational" decision-making. This capacity is vulnerable in neuropsychiatric disorders and inthe aftermath of chronic stress, in which aberrantchoices and high-risk behaviors occur. Wereport that chronic stress exposure in rodents produces abnormal evaluation of costs and benefitsresembling non-optimal decision-making in whichchoicesof high-cost/high-reward options are sharply increased. Concomitantly, alterations in the task-related spike activity of medial prefrontal neurons correspond with increased activity of their striosome-predominant striatal projection neuron targets and with decreased and delayed striatal fast-firing interneuron activity. These effects of chronic stress on prefronto-striatal circuit dynamics could be blocked or be mimicked by selective optogenetic manipulation of these circuits. We suggest that altered excitation-inhibition dynamics of striosome-based circuit function could be an underlying mechanism by which chronic stress contributes to disorders characterized by aberrant decision-making under conflict. VIDEO ABSTRACT.