AbstractPursuing rewards while avoiding danger is an essential function of nervous systems. Here, we examine a new mechanism helping rats negotiate the balance between risk and reward when making high-stakes decisions. Specifically, we focus on GABA neurons within an emerging mesolimbic circuit nexus, the ventral pallidum (VP). These neurons play a distinct role from other VP neurons in simple motivated behaviors in mice, but their roles in more complex motivated behaviors is unknown. Here, we interrogate the behavioral functions of VPGABA neurons in male and female transgenic GAD1:Cre rats (and wildtype littermates), using reversible chemogenetic inhibition. Employing a behavioral assay of risky decision making, and of the food-seeking and shock-avoidance components of this task, we show that engaging inhibitory Gi/o signaling specifically in VPGABA neurons suppresses motivation to pursue highly salient palatable foods, and notably, also motivation to avoid being shocked. In contrast, inhibiting these neurons did not affect seeking of low-value food, or free consumption even of palatable food, nor did it impact unconditioned affective responses to shock. Accordingly, when rats considered whether to pursue food despite potential for shock in a risky decision-making task, inhibiting VPGABA neurons caused rats to more readily select a small but safe reward over a large but dangerous one—the first demonstration of a VP role in complex decision making. Together, results indicate that VPGABA neurons are critical for high-stakes adaptive responding that is necessary for life, but which might also malfunction in psychiatric disease.Significance StatementIn a dynamic world, it is essential to implement appropriate behaviors under circumstances involving rewards, threats, or both. Here, we demonstrate a crucial role for VPGABA neurons in high-stakes motivated behavior, both in pursuit of highly valued rewards, and to avoid perceived threats. We also show that this VPGABA role in motivation impacts cognition, as inhibition of these neurons yields a conservative, risk-averse decision-making strategy. These new roles for VPGABA neurons in behavior may inform future strategies for treating addiction, and other disorders of maladaptive decision making.
Ventral Pallidum GABA Neurons Mediate Motivation Underlying Risky Choice
