Neurobiological investigation of delay discounting: role of prelimbic cortex -> nucleus accumbens circuit

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Project Summary/Abstract Delay discounting is a type of decision-making in which individuals discount the value of a reward based on the amount of delay to its receipt [1-4]. Generally, individuals will wait for a larger reward when there is a short delay. However, as delay to reward increases, individuals will shift their preference toward the smaller, immediate reward and in this way, delay discounting serves as a measure of impulsivity [1, 2, 4]. Importantly, heightened delay discounting (increased impulsivity) is a common symptom of substance use disorders [5-8]. Drugs of abuse such as cocaine decrease the point at which individuals shift to the small, immediate reward, resulting in more impulsive behavior [6, 8, 16-18]. As such, increased impulsivity may promote the selection of short-term rewards of continued drug use over long-term benefits (e.g., health, jobs, family) associated with drug abstinence. Critically, these findings are corroborated in rodent models, as prior exposure to cocaine increases impulsivity during decision making tasks involving delay, magnitude, and delay discounting [2, 19, 20]. Further, gender differences exist in delay discounting, with some data indicating that females demonstrate heightened impulsivity (compared to males) during a delay discounting task in rodents [23-25], and in humans [21, 22]. As such, it is critical to understand the neural underpinnings of delay discounting behavior, and potential gender differences in this process. In this regard, the prelimbic cortex (PrL) and nucleus accumbens (NAc) are implicated in impulsive behavior and choice [26, 27] and represent a key neural circuit in delay discounting behavior. Importantly, the PrL selectively enervates the NAc core [28-32]. However, no studies have directly examined the activity of PrL neurons during delay discounting behavior in male or female rats, or if the PrL-NAc core circuit is causally linked to this behavior. Two specific aims are proposed in this application to address these topics. Aim 1 will use multi-neuron recording methods to examine how neurons in the PrL encode information about the important features of delay discounting behavior while animals are actively engaged in a well-established delay discounting task. Aim 2 will build upon that work and use optogenetic tools to investigate a potential causal role of the PrL-NAc core pathway in delay discounting behavior. Collectively, these studies will provide critical insight into the functional role of the PrL-NAc core circuit in delay discounting behavior across genders and set the foundation for future studies that can examine how drugs of abuse alter this system and contribute to maladaptive decision making behaviors.