Taira Masakazu, Miyazaki Kayoko W, Miyazaki Katsuhiko, Chen Jianning, Okitsu-Sakurayama Shiho, Chaudhary Anupama, Nishio Mika, Miyake Tsukasa, Yamanaka Akihiro, Tanaka Kenji F, Doya Kenji
Neural Computation Unit, Okinawa Institute of Science and Technology Graduate University, Okinawa, Japan.
Department of Psychology, University of Sydney, Camperdown, NSW, Australia.
Front Neurosci. 2024 Sep 25;18:1433061. doi: 10.3389/fnins.2024.1433061. eCollection 2024.
Serotonin is an essential neuromodulator that affects behavioral and cognitive functions. Previous studies have shown that activation of serotonergic neurons in the dorsal raphe nucleus (DRN) promotes patience to wait for future rewards. However, it is still unclear whether serotonergic neurons also regulate persistence to act for future rewards. Here we used optogenetic activation and inhibition of DRN serotonergic neurons to examine their effects on sustained motor actions for future rewards. We trained mice to perform waiting and repeated lever-pressing tasks with variable reward delays and tested effects of optogenetic activation and inhibition of DRN serotonergic neurons on task performance. Interestingly, in the lever-pressing task, mice tolerated longer delays as they repeatedly pressed a lever than in the waiting task, suggesting that lever-pressing actions may not simply be costly, but may also be subjectively rewarding. Optogenetic activation of DRN serotonergic neurons prolonged waiting duration in the waiting task, consistent with previous studies. However, its effect on lever presses was nuanced, and was detected only by focusing on the period before premature reward check and by subtracting the trends within and across sessions using generalized linear model. While optogenetic inhibition decreased waiting, it did not affect lever pressing time or numbers. These results revealed that the necessity of motor actions may increase motivation for delayed rewards and that DRN serotonergic neurons more significantly promote waiting rather than persistent motor actions for future rewards.
血清素是一种影响行为和认知功能的重要神经调节剂。先前的研究表明，中缝背核（DRN）中血清素能神经元的激活会增强等待未来奖励的耐心。然而，血清素能神经元是否也调节为未来奖励而行动的坚持性仍不清楚。在这里，我们使用光遗传学激活和抑制DRN血清素能神经元，以研究它们对为未来奖励而持续进行的运动行为的影响。我们训练小鼠执行等待和重复压杆任务，奖励延迟可变，并测试光遗传学激活和抑制DRN血清素能神经元对任务表现的影响。有趣的是，在压杆任务中，小鼠在反复压杆时比在等待任务中能忍受更长的延迟，这表明压杆动作可能不仅仅代价高昂，而且在主观上也可能是有回报的。DRN血清素能神经元的光遗传学激活延长了等待任务中的等待持续时间，这与先前的研究一致。然而，它对压杆的影响是细微的，只有通过关注过早检查奖励之前的时间段，并使用广义线性模型减去各次实验内和各次实验间的趋势才能检测到。虽然光遗传学抑制减少了等待时间，但它并不影响压杆时间或次数。这些结果表明，运动行为的必要性可能会增加对延迟奖励的动机，并且DRN血清素能神经元更显著地促进等待，而不是为未来奖励而持续进行的运动行为。
