Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan.
Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka Metropolitan University, 1-4-3 Asahi-cho, Abeno-ku, Osaka, 545-8585, Japan.
Nat Commun. 2022 Dec 22;13(1):7708. doi: 10.1038/s41467-022-35346-7.
Appropriate processing of reward and aversive information is essential for survival. Although a critical role of serotonergic neurons in the dorsal raphe nucleus (DRN) in reward processing has been shown, the lack of rewarding effects with selective serotonin reuptake inhibitors (SSRIs) implies the presence of a discrete serotonergic system playing an opposite role to the DRN in the processing of reward and aversive stimuli. Here, we demonstrated that serotonergic neurons in the median raphe nucleus (MRN) of mice process reward and aversive information in opposite directions to DRN serotonergic neurons. We further identified MRN serotonergic neurons, including those projecting to the interpeduncular nucleus (5-HT), as a key mediator of reward and aversive stimuli. Moreover, 5-HT receptors, including 5-HT receptors in the interpeduncular nucleus, are involved in the aversive properties of MRN serotonergic neural activity. Our findings revealed an essential function of MRN serotonergic neurons, including 5-HT, in the processing of reward and aversive stimuli.
适当处理奖励和厌恶信息对生存至关重要。尽管已经表明背侧中缝核（DRN）中的 5-羟色胺能神经元在奖励处理中起着关键作用，但选择性 5-羟色胺再摄取抑制剂（SSRIs）缺乏奖励作用表明存在离散的 5-羟色胺能系统，在处理奖励和厌恶刺激方面与 DRN 中的 5-羟色胺能神经元起着相反的作用。在这里，我们证明了小鼠中缝核中间部（MRN）的 5-羟色胺能神经元以与 DRN 5-羟色胺能神经元相反的方向处理奖励和厌恶信息。我们进一步确定了 MRN 5-羟色胺能神经元，包括投射到脚间核（5-HT）的神经元，作为奖励和厌恶刺激的关键介导者。此外，5-羟色胺受体，包括脚间核中的 5-羟色胺受体，参与了 MRN 5-羟色胺能神经活动的厌恶特性。我们的发现揭示了 MRN 5-羟色胺能神经元，包括 5-HT，在处理奖励和厌恶刺激中的重要功能。
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