Basolateral Amygdala Projections to the Prelimbic Cortex Suppress the Motivational Value of Reward-Associated Cues

Reward-associated cues drive reward-seeking behaviours, with different cue types taking on distinct associative meanings. In instrumental settings, discriminative stimuli (DSs) signal when a response will produce reward, while conditioned stimuli (CSs) are paired with reward delivery after responding. Basolateral amygdala (BLA) projections are known to mediate CS-guided reward seeking, but their role in DS-guided behaviour remains unclear despite DSs being uniquely effective in triggering reward seeking. Here, we used optogenetic stimulation of BLA projections to the nucleus accumbens (NAc) core or prelimbic cortex (PrL) to probe their causal involvement in DS- and CS-guided sucrose seeking. Female and male rats learned to lever press during DS+ trials to obtain sucrose paired with a CS+, and to withhold responding during DS- trials where sucrose was unavailable. We then assessed sucrose seeking evoked by response-independent DS+ and CS+ presentations, without sucrose. The DS+ prompted the greatest increases in lever pressing, acting as a strong Pavlovian conditioned excitor. Cue-paired photostimulation of BLA[->]NAc core or BLA[->]PrL projections did not alter this effect. In a test of instrumental responding for conditioned reinforcement, rats lever pressed most for DS+ and CS+ presentations, with no effect of cue-type, indicating that the two cues gained comparable conditioned reinforcing value. While cue-paired photostimulation of BLA[->]NAc core neurons had no impact, photostimulation of BLA[->]PrL projections suppressed instrumental responding for both the DS+ and CS+. These findings reveal the BLA[->]PrL pathway as a key regulator that constrains control over behaviour by reward-associated cues, making them less desirable and reducing their motivational effects.