Basolateral Amygdala Drives a GPCR-Mediated Striatal Memory Necessary for Predictive Learning to Influence Choice

Predictive learning exerts a powerful influence over choice between instrumental actions. Nevertheless, how this learning is encoded in a sufficiently stable manner to influence choices that can occur much later in time is unclear. Here, we report that the basolateral amygdala (BLA) encodes predictive learning and establishes the memory necessary for future choices by driving the accumulation of delta-opioid receptors (DOPRs) on the somatic membrane of cholinergic interneurons in the nucleus accumbens shell (NAc-S). We found that the BLA controls DOPR accumulation via its influence on substance P release in the NAc-S, and that although DOPR accumulation is not necessary for predictive learning per se, it is necessary for the influence of this learning on later choice between actions. This study uncovers, therefore, a novel GPCR-based form of memory that is established by predictive learning and is necessary for such learning to guide the selection and execution of specific actions.