Review: "The Disappointment Dilemma: Short- and Long-Term Learning From Negative Outcomes".

In this review, we synthesize key findings from the 2025 Spanish Society for Neuroscience (SENC) symposium "Understanding Habenulae Function in Emotional Behavior" and propose that the brain possesses a "disappointment circuit" that complements the classic dopaminergic reward system. The "disappointment dilemma" in financial investing-avoiding risk to prevent short-term disappointment, only to later experience greater long-term disappointment when safe choices underperform-illustrates how immediate and delayed negative outcomes can be traded off over time. We argue that this dilemma parallels partially specialized roles of the lateral habenula (LHb), which signals immediate disappointments as acute negative prediction errors, and the medial habenula (MHb), which shapes longer-lasting negative expectations or mood through the accumulation of disappointing experiences over time. We propose that LHb outputs implement fast, trial-by-trial adjustments in coping strategies via RMTg- and VTA-projecting pathways, whereas MHb-IPN circuits gradually reshape threat valuation, withdrawal states, and mood across repeated disappointing or stressful experiences. We discuss how LHb and MHb circuits contribute to short- and long-term disappointment by integrating information on stress resilience, aversive learning, threat and fear responses, drug-related behaviors, and mood adaptation from specific cell types and receptors that modulate fear, addiction, and motivation to circuit-level mechanisms underlying aversive learning and emotional responses.