Separate prefrontal-subcortical circuits mediate different components of risk-based decision making

Abstract

Choosing between smaller, assured rewards or larger, uncertain ones requires reconciliation of competing biases toward more certain or riskier options. We used disconnection and neuroanatomical techniques to reveal that separate, yet interconnected, neural pathways linking the medial prefrontal cortex (PFC), the basolateral amygdala (BLA), and nucleus accumbens (NAc) contribute to these different decision biases in rats. Disrupting communication between the BLA and NAc revealed that this subcortical circuit biases choice toward larger, uncertain rewards on a probabilistic discounting task. In contrast, disconnections between the BLA and PFC increased choice of the Large/Risky option. PFC-NAc disconnections did not affect choice but did increase choice latencies and trial omissions. Neuroanatomical studies confirmed that projection pathways carrying axons from BLA-to-PFC transverse a distinctly different route relative to PFC-to-BLA pathways (via the ventrolateral amydalofugal pathway and ventromedial internal capsule, respectively). We exploited these dissociable axonal pathways to selectively disrupt bottom-up and top-down communication between the BLA and PFC. Subsequent disconnection studies revealed that disruption of top-down (but not bottom-up) information transfer between the medial PFC and BLA increased choice of the larger, riskier option, suggesting that this circuit facilitates tracking of actions and outcomes to temper urges for riskier rewards as they become less profitable. These findings provide novel insight into the dynamic competition between these cortical/subcortical circuits that shape our decision biases and underlie conflicting urges when evaluating options that vary in terms of potential risks and rewards.

Figure 1.

Probabilistic discounting task design. A, Cost/benefit contingencies associated with responding on either lever. B, Format of the sequence of forced and free choice trials within each probability block of a training session. C, Format of a single free-choice trial.

Figure 2.

Disconnection of the BLA–NAc pathway reduces choice of the Large/Risky option, but does not affect reward magnitude discrimination. A, Percentage choice of the Large/Risky lever following disconnection of the NAc and BLA and control treatments across four blocks of free-choice trials. Symbols represent mean, error bars are SEM. Black star denotes p < 0.05 for the average choice from ipsilateral/disconnection versus saline. Inset shows data from a subset of rats that did not show a decrease in risky choice after ipsilateral inactivation (n = 7), yet still showed a decrease in risky choice following functional disconnection (star denotes p < 0.05). B, Schematic of sections of the rat brain showing location of acceptable infusions in the NAc and BLA for rats in discounting (circles) and magnitude discrimination (squares) experiments. Numbers correspond to millimeters from bregma. Figure represents the disconnection procedure for clarity; hemispheres of infusions were counterbalanced across rats. C, Win–stay/lose–shift ratios following saline infusions, ipsilateral, and functional disconnection (asymmetrical inactivation) of the BLA–NAc pathway. Win–stay values are displayed as the proportion of choices on the Large/Risky lever following a rewarded risky choice on the preceding trial. Lose–shift values are displayed as the proportion of choices on the Small/Certain lever following unrewarded risky choice on the preceding trial. Neither of these measures were significantly altered by BLA–NAc disconnections. D, Disrupting communication in this pathway had no effect on preference for larger versus smaller rewards on a simpler reward magnitude discrimination. Inset shows response latencies to press the large or small reward lever on forced choice trials after saline infusions for rats trained on the reward magnitude discrimination or the probabilistic discounting task. Rats trained on the latter showed a smaller difference between latencies to press the larger versus smaller reward lever compared with those trained on the simpler magnitude discrimination (star denotes p < 0.01).

Figure 3.

Disconnection of the medial PFC–BLA pathway increased choice of Large/Risky option. A, Choice for the Large/Risky lever following medial PFC–BLA disconnections and control treatments. Open star, p < 0.05 saline versus functional disconnection; *p < 0.05 (ipsilateral vs disconnection). B, Win–stay/lose–shift data. Disconnection of the medial PFC–BLA pathway decreased negative feedback sensitivity, reducing the tendency to choose the certain option after a nonrewarded risky choice ⁺p = 0.059. C, Acceptable location of infusions through the rostral–caudal extent of the medial PFC and BLA.

Figure 4.

Disconnecting the medial PFC and NAc does not affect probabilistic discounting. A, Left, Choice for the Large/Risky lever following medial PFC–NAc disconnections and control treatments. Right, Acceptable location of infusions through the rostral–caudal extent of the medial PFC and NAc. B, C, Disconnection of this pathway increased choice latencies (B) and trial omissions (C). Sal, Saline; Ipsi, ipsilateral; Disc, disconnection. *p < 0.05 versus saline.

Figure 5.

A–I, Diagrams of sections of rat brain ordered from rostral to caudal levels and indicating anterograde labeling produced by an injection of the anterograde tracer biotinylated dextran amine into the BLA, represented by the blue dots in I. Labeled fibers are represented by short lines, which indicate directional orientation, and areas with dense terminal-like labeling are indicated by fine stippling. The pathway from the BLA to the medial prefrontal cortex is highlighted in blue and the site where bupivacaine was infused in the present study to inactivate the pathway is circled in red (D). AC, Anterior cingulate cortex; Acb, nucleus accumbens; BST, bed nucleus of stria terminalis; CeA, central nucleus of the amygdala; CPu, caudate–putamen; ec, external capsule; PL, prelimbic cortex; SLEA, sublenticular extended amygdala; st, stria terminalis; vap, ventral amygdalofugal pathway.

Figure 6.

A–I, Diagrams of sections of rat brain ordered from rostral to caudal levels and indicating anterograde labeling produced by an injection of the anterograde tracer Phaseolus vulgaris leucoagglutinin into the prelimbic cortex (PL), represented by the red dots in A. Labeled fibers are represented by short lines, which indicate directional orientation, and areas with dense terminal-like labeling are indicated by fine stippling. The pathway from the medial PFC to the basolateral amygdala is highlighted in red and the site where bupivacaine was infused in the present study to inactivate the pathway is circled in blue (G). Acb, Nucleus accumbens; BST, bed nucleus of stria terminalis; CeA, central nucleus of the amygdala; CPu, caudate–putamen; GP, globus pallidus; ic, internal capsule; SLEA, sublenticular extended amygdala; st, stria terminalis.

Figure 7.

Summary diagram displaying the routes that ascending and descending axons in BLA–PFC pathways take through different sections of the rat brain, highlighting the regions targeted for bupivacaine infusions in disconnection experiments targeting the ascending and descending BLA–PFC pathways.

Figure 8.

Effect of disconnecting ascending and descending pathways between the medial PFC and BLA on probabilistic discounting. A, Ascending BLA→PFC pathway. Left, Choice for the Large/Risky lever following disconnection of the PFC and ventrolateral amydalofugal pathway and control treatments. Disconnection of the ascending pathway had no effect on choice. Right, Acceptable location of infusions in the PFC and ventrolateral edge of the corpus callosum. B, Descending PFC→BLA pathway. Left, In contrast, disconnection of the descending pathway increased Large/Risky choice. *p < 0.05, disconnection versus saline. Right, Acceptable location of infusions in BLA and ventromedial internal capsule. C, Win–stay and lose–shift data for descending pathway disconnections. Black star denotes a significant difference from saline, p < 0.05. Increased risky choice after disconnection of the descending pathway was attributable to a reduced sensitivity to reward omissions (decreased lose–shift performance).