PT - JOURNAL ARTICLE AU - Keefer, Sara E. AU - Kochli, Daniel E. AU - Calu, Donna J. TI - Inactivation of the Basolateral Amygdala to Insular Cortex Pathway Makes Sign-Tracking Sensitive to Outcome Devaluation AID - 10.1523/ENEURO.0156-22.2022 DP - 2022 Sep 01 TA - eneuro PG - ENEURO.0156-22.2022 VI - 9 IP - 5 4099 - http://www.eneuro.org/content/9/5/ENEURO.0156-22.2022.short 4100 - http://www.eneuro.org/content/9/5/ENEURO.0156-22.2022.full SO - eNeuro2022 Sep 01; 9 AB - Goal-tracking (GT) rats are sensitive to Pavlovian outcome devaluation while sign-tracking (ST) rats are devaluation insensitive. During outcome devaluation, GT rats flexibly modify responding to cues based on the current value of the associated outcome. However, 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 GT and ST 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 before brief nonreinforced 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.