Identifying the neurophysiological basis of risky decision-making

University Of Memphis, Memphis TN

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Abstract

Abstract Drug addiction is associated with pathological risk-taking behavior, which engenders ongoing drug-seeking despite the risk of consequences. Animal models are necessary to clarify the specific neuronal substrates underlying risky decision-making, with the goal of understanding how aberrant neuronal activity contributes to suboptimal choice in addiction. The rat risky decision-making task (RDT) models this behavior by measuring preference between small, safe rewards and larger rewards accompanied by an escalating probability of an aversive event (shock). However, little is known about the neuronal mechanisms that compel these subjects toward persistent insensitivity to consequences. Does the brain of a risk-taker process information differently than the rest of the population during the deliberation point preceding a decision? Alternatively, is this behavior driven by an inability to effectively encode the integration of rewards with consequences? Here, we will address these and other fundamental questions about the mechanisms underlying risk-taking by incorporating specially designed behavioral tasks with single unit electrophysiology. Preliminary data suggest that risky decision-making is mediated by distinct regions of striatum and prefrontal cortex. Informed by these data, we will implant electrodes bilaterally into either nucleus accumbens (NAC) shell, NAC core, dorsal striatum, medial prefrontal cortex, orbitofrontal cortex, or insular cortex. Our aims will focus on how patterns of functional activity in these brain regions differ between subjects predisposed to risky behavior and the rest of the population. In Aim 1, we will record activity during a modified version of RDT that requires the rat to hold a nose-poke for one second prior to each decision, which allows assessment of neuronal activity immediately prior to a decision that is not confounded by differences in behavior. In Aim 2, rats will train in Pavlovian Conditioning with both rewarding and aversive stimuli, followed by a probe session in which rats are exposed to either cue individually, as well as a compound cue during which both are presented simultaneously. By recording functional neuronal activity during this session, we can measure of the mental representations evoked by rewarding and aversive cues, as well as the ability to integrate this information. Contrasting these neurophysiological data between risk-taking and risk-averse rats will further elucidate the mechanisms underlying a behavioral tendency highly relevant to addiction vulnerability. Collectively, these data will help identify the biological mechanisms that promote compulsive reward seeking in the face of punishment, a critical component of addiction. In addition, a priority of this proposal is to expose undergraduate students to meritorious research utilizing complex behavior and cutting-edge electrophysiological techniques.