Periaqueductal gray passes over disappointment and signals continuity of remaining reward expectancy.

Disappointment is a vital factor in the learning and adjustment of strategies in reward-seeking behaviors. It helps them conserve energy in environments where rewards are scarce, while also increasing their chances of maximizing rewards by prompting them to escape to environments where richer rewards are anticipated (e.g., migration). However, another key factor in obtaining the reward is the ability to monitor the remaining possibilities of obtaining the outcome and to tolerate the disappointment in order to continue with subsequent actions. The periaqueductal gray (PAG) has been reported as one of the key brain regions in regulating negative emotions and escape behaviors in animals. The present study suggests that the PAG could also play a critical role in inhibiting escape behaviors and facilitating ongoing motivated behaviors to overcome disappointing events. We found that PAG activity is tonically suppressed by reward expectancy as animals engage in a task to acquire a reward outcome. This tonic suppression of PAG activity was sustained during a series of sequential task procedures as long as the expectancy of reward outcomes persisted. Notably, the tonic suppression of PAG activity showed a significant correlation with the persistence of animals' reward-seeking behavior while overcoming intermittent disappointing events. This finding highlights that the balance between distinct tonic signaling in the PAG, which signals remaining reward expectancy, and phasic signaling in the lateral habenula, which signals disappointment, could play a crucial role in determining whether animals continue or discontinue reward-seeking behaviors when they encounter an unexpected negative event. This mechanism would be essential for animals to efficiently navigate complex environments with various reward volatilities and ultimately contributes to maximizing their reward acquisition.