Lee Hyunchan, Hikosaka Okihide
Laboratory of Sensorimotor Research, National Eye Institute, National Institutes of Health, Bethesda, MD 20892-4435, USA.
Res Sq. 2025 Feb 13:rs.3.rs-2720067. doi: 10.21203/rs.3.rs-2720067/v1.
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.
失望是奖励寻求行为中学习和策略调整的一个重要因素。它有助于动物在奖励稀缺的环境中保存能量，同时通过促使它们逃向预期有更丰富奖励的环境（如迁徙）来增加它们获得最大奖励的机会。然而，获得奖励的另一个关键因素是监测获得结果的剩余可能性并容忍失望以便继续后续行动的能力。中脑导水管周围灰质（PAG）已被报道为调节动物负面情绪和逃避行为的关键脑区之一。本研究表明，PAG在抑制逃避行为和促进持续的动机行为以克服令人失望的事件方面也可能发挥关键作用。我们发现，当动物参与获取奖励结果的任务时，PAG活动会因奖励预期而受到持续性抑制。只要奖励结果的预期持续存在，在一系列连续的任务过程中，PAG活动的这种持续性抑制就会持续。值得注意的是，PAG活动的持续性抑制与动物在克服间歇性令人失望的事件时奖励寻求行为的持续性呈显著相关。这一发现突出表明，PAG中发出剩余奖励预期信号的不同持续性信号与外侧缰核中发出失望信号的相位性信号之间的平衡，在决定动物在遇到意外负面事件时是继续还是停止奖励寻求行为方面可能起着关键作用。这种机制对于动物在具有各种奖励波动性的复杂环境中有效导航至关重要，并最终有助于最大化它们的奖励获取。
