Inactivation of the basolateral amygdala to insular cortex pathway makes sign-tracking sensitive to outcome devaluation.

Goal-tracking rats are sensitive to Pavlovian outcome devaluation while sign-tracking rats are devaluation insensitive. During outcome devaluation, goal-tracking (GT) rats flexibly modify responding to cues based on the current value of the associated outcome. However, sign-tracking (ST) rats rigidly respond to cues regardless of the current outcome value. Prior work demonstrated disconnection of the basolateral amygdala (BLA) and anterior insular cortex (aIC) decreased both goal- and sign-tracking behaviors. Given the role of these regions in appetitive motivation and behavioral flexibility we predicted that disrupting BLA to aIC pathway during outcome devaluation would reduce flexibility in GT rats and reduce rigid appetitive motivation in ST rats. We inhibited the BLA to aIC pathway by infusing inhibitory DREADDs (hM4Di-mcherry) or control (mCherry) virus into the BLA and implanted cannulae into the aIC to inhibit BLA terminals using intracranial injections of clozapine N-oxide (CNO). After training, we used a within - subject satiety-induced outcome devaluation procedure in which we sated rats on training pellets (devalued condition) or homecage chow (valued condition). All rats received bilateral CNO infusions into the aIC prior to brief non-reinforced test sessions. Contrary to our hypothesis, BLA-IC inhibition did not interfere with devaluation sensitivity in GT rats but did make ST behaviors sensitive to devaluation. Intermediate rats showed the opposite effect, showing rigid responding to cues with BLA-aIC pathway inactivation. Together, these results demonstrate BLA-IC projections mediate tracking-specific Pavlovian devaluation sensitivity and highlights the importance of considering individual differences in Pavlovian approach when evaluating circuitry contributions to behavioral flexibility. Significance Statement Individual differences in sign- and goal-tracking behavior are characterized by differences in motivational properties towards reward predictive cues, which can predict differences in behavioral flexibility and addiction-related behaviors. Goal-trackers flexibly adjust their behavior when the value of outcomes change, while sign-trackers rigidly respond to cues after devaluation of the outcome. Preclinical research indicates neurobiological differences between sign- and goal-tracking individuals, resulting in behavioral differences prior to drug use and addiction. The current study tested the hypothesis that tracking-specific differences in utilization of an amygdala-cortical circuitry contributes to behavioral flexibility differences. This work ultimately furthers our understanding of the behavioral and neurobiological underpinnings of individual differences in adaptive behaviors and addiction vulnerability.