The role of the amygdala-striatal pathway in the acquisition and performance of goal-directed instrumental actions

Abstract

The posterior dorsomedial striatum (pDMS) is essential for the acquisition and expression of the specific response-outcome (R-O) associations that underlie goal-directed action. Here we examined the role of a pathway linking the basolateral amygdala (BLA) and pDMS in such goal-directed learning. In Experiment 1, rats received unilateral lesions of the BLA and were implanted with cannula targeting the pDMS in either the ipsilateral (control) or contralateral (disconnection) hemisphere. After initial training, rats received infusions of muscimol to inactivate the pDMS immediately before sessions in which novel R-O associations were introduced. Sensitivity to devaluation by specific satiety was then assessed. Whereas rats in the ipsilateral group used the recently acquired associations to direct performance following devaluation, those in the contralateral group could not, indicating that BLA-pDMS disconnection prevented the acquisition of the new R-O associations. Indeed, evidence suggested that these rats relied instead on learning acquired during prior training to direct performance following devaluation. In Experiment 2, rats underwent similar surgery and training except they received muscimol infusions immediately before devaluation testing. Those in the ipsilateral group showed a selective devaluation effect, again based on the most recently introduced R-O associations. In contrast, rats in the contralateral group showed nonselective performance after devaluation indicating that the BLA-DMS pathway is also required for the expression of selective R-O associations. Together these results suggest that input from the BLA is essential for specific R-O learning by the pDMS.

Figure 1.

A, Mean lever presses for the left and right lever for the final day of training with a common reward (polycose), with the introduction of novel R–O contingences (left lever–pellet; right lever–sucrose), and the reversal of those contingencies (left lever–sucrose; right lever–pellets). B, Mean lever presses following devaluation by specific satiety. Devalued refers to responding on the lever most recently paired with the pre-fed outcome. Non-devalued refers to responding on the lever most recently earning the alternate outcome. Asterisk indicates that responding on the devalued lever differed significantly from responding on the non-devalued lever, p < 0.05. C, Mean (±SE) c-Fos-positive, FG-positive, and double-labeled cells in the BLA following devaluation testing.

Figure 2.

A, A representative example of the FG injection site in the pDMS and the pattern of FG that was retrogradely transported to the BLA (B). Panel C shows the region of the BLA that is magnified in panels D-F below. D, FG positive cells in the BLA. The white inset indicates the region that is further magnified in panels D'-F'. E, c-Fos positive cells in the BLA. F, Coexpression of FG and c-Fos in the BLA. (D'-F') Magnification of panels D-F above.

Figure 3.

Schematic representation of lesions to the BLA (right) and cannula placements in the pDMS (left) for rats in Experiments 2 and 3. Note that for rats in the ipsilateral groups, lesions and cannula were in the same hemisphere whereas for rats in the contralateral groups, lesions and cannula were in opposite hemispheres. Light gray indicates the maximum damage and dark gray indicates the minimum damage for rats included in the behavioral analyses. Damage typically extended from −2.3 to −3.2 mm relative to bregma, with some subjects showing evidence of damage slightly further rostrally or caudally, and typically included the majority of the lateral, basal, and accessory basal divisions of the region. There was some sparing of tissue in the more ventral and medial regions as well in the most caudal areas of the BLA. Cannula were positioned in the pDMS striatum typically between +0.2 to −0.3 mm from bregma. Numbers indicate distance (mm) from bregma. Based on Paxinos and Watson, 1998.

Figure 4.

A, Schematic representation of the experimental design for Experiment 1. Rats underwent surgery to lesion the BLA and implant cannulae targeting the pDMS. They were then trained to perform two instrumental responses, each earning a common reward (polycose). The next underwent two training sessions in which each response earned a unique outcome. These R-O contingencies were reversed in two subsequent sessions and critically, the pDMS was inactivated before these sessions. One of the two instrumental outcomes was then devalued with a specific satiety procedure before a 5 min extinction test. B, Mean lever presses for the left and right lever for rats in the ipsilateral (ipsi) and contralateral (contra) groups on the final day of training with a common reward (polycose), with the introduction of novel R–O contingences (left lever–pellet; right lever–sucrose), and the reversal of those contingencies (left lever–sucrose; right lever–pellets). Note that rats received infusions of muscimol before the last two training sessions. C, Mean lever presses following devaluation by specific satiety. Devalued refers to responding on the lever most recently paired with the pre-fed outcome. Non-devalued refers to responding on the lever most recently earning the alternate outcome. Asterisk indicates that responding on the devalued lever differed significantly from responding on the non-devalued lever, p < 0.05. There were no infusions before testing.

Figure 5.

A, Schematic representation of the experimental design for Experiment 2. Rats underwent surgery to lesion the BLA and implant cannulae targeting the pDMS. They were then trained to perform two instrumental responses, each earning a common reward (polycose). The next underwent two training sessions in which each response earned a unique outcome. These R–O contingencies were reversed in two subsequent sessions. Finally, one of the two instrumental outcomes was devalued with a specific satiety procedure and, critically, the pDMS was inactivated immediately before a 5 min extinction test. B, Mean lever presses for the left and right lever for rats in the ipsilateral (ipsi) and contralateral (contra) groups on the final day of training with a common reward (polycose), with the introduction of novel R–O contingences (left lever–pellet; right lever–sucrose), and the reversal of those contingencies (left lever–sucrose; right lever–pellets). C, Mean lever presses following devaluation by specific satiety. Note that rats received infusions of muscimol after the prefeeding and before being placed in the operant chambers for testing. Devalued refers to responding on the lever most recently paired with the pre-fed outcome. Non-devalued refers to responding on the lever most recently earning the alternate outcome. Asterisk indicates that responding on the devalued lever differed significantly from responding on the non-devalued lever, p < 0.05.

Figure 6.

Mean milliliters of sucrose consumed following 1 h ad libitum access to either sucrose (same; devalued) or pellets (different; non-devalued). Note that the rats received an infusion of muscimol after pre-feeding and before introduction of the test food. Asterisk indicates that consumption following prefeeding of the same outcome (devalued) differed from that following prefeeding of a different outcome (non-devalued), p < 0.05.