Circuit and Cell-Specific Contributions to Decision Making Involving Risk of Explicit Punishment in Male and Female Rats.

Decision making is a complex cognitive process that recruits a distributed network of brain regions, including the basolateral amygdala (BLA) and nucleus accumbens shell (NAcSh). Recent work suggests that communication between these structures, as well as activity of cells expressing dopamine (DA) D2 receptors (D2R) in the NAcSh, are necessary for some forms of decision making; however, the contributions of this circuit and cell population during decision making under risk of punishment are unknown. The current experiments addressed this question using circuit-specific and cell type-specific optogenetic approaches in rats during a decision making task involving risk of punishment. In experiment 1, Long-Evans rats received intra-BLA injections of halorhodopsin or mCherry (control) and in experiment 2, D2-Cre transgenic rats received intra-NAcSh injections of Cre-dependent halorhodopsin or mCherry. Optic fibers were implanted in the NAcSh in both experiments. Following training in the decision making task, BLA→NAcSh or D2R-expressing neurons were optogenetically inhibited during different phases of the decision process. Inhibition of the BLA→NAcSh during deliberation (the time between trial initiation and choice) increased preference for the large, risky reward (increased risk taking). Similarly, inhibition during delivery of the large, punished reward increased risk taking, but only in males. Inhibition of D2R-expressing neurons in the NAcSh during deliberation increased risk taking. In contrast, inhibition of these neurons during delivery of the small, safe reward decreased risk taking. These findings extend our knowledge of the neural dynamics of risk taking, revealing sex-dependent circuit recruitment and dissociable activity of selective cell populations during decision making. Until recently, the ability to dissect the neural substrates of decision making involving risk of punishment (risk taking) in a circuit-specific and cell-specific manner has been limited by the tools available for use in rats. Here, we leveraged the temporal precision of optogenetics, together with transgenic rats, to probe contributions of a specific circuit and cell population to different phases of risk-based decision making. Our findings reveal basolateral amygdala (BLA)→nucleus accumbens shell (NAcSh) is involved in evaluation of punished rewards in a sex-dependent manner. Further, NAcSh D2 receptor (D2R)-expressing neurons make unique contributions to risk taking that vary across the decision making process. These findings advance our understanding of the neural principles of decision making and provide insight into how risk taking may become compromised in neuropsychiatric diseases.