Kawai Hiroyuki
Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University.
Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka Metropolitan University.
Yakugaku Zasshi. 2025;145(2):79-84. doi: 10.1248/yakushi.24-00150.
Serotonergic neurons play a critical role in processing reward and aversive information. Rewarding stimuli activate serotonergic neurons in the dorsal raphe nucleus (DRN), whereas optogenetic activation of DRN serotonergic neurons induces reward-like effects. However, the pharmacological enhancement of serotonin neurotransmission does not induce rewarding or aversive effects. These findings suggest the presence of another serotonergic neuron that plays a role opposite to that of the DRN in processing reward and aversion information. Previous reports suggested that the median raphe nucleus (MRN) processes negative emotional stimuli. To elucidate the function of MRN serotonergic neurons in these processes, we recorded the changes in serotonergic activity in mice in response to rewarding and aversive stimuli. We also used optogenetic manipulation to determine whether these changes could induce rewarding and aversive behaviors. The activity of MRN serotonergic neurons decreased in response to rewarding stimuli and increased after aversive stimuli. Optogenetic inhibition of MRN serotonergic neurons induced reward-related behavior, while optogenetic stimulation induced aversion-related behavior. Furthermore, we found that the projection pathway from MRN serotonergic neurons to the interpeduncular nucleus is crucial for these processes. These results indicate that MRN serotonergic neurons play a pivotal role in processing reward and aversive information, functioning oppositely to DRN neurons.
血清素能神经元在处理奖赏和厌恶信息方面发挥着关键作用。奖赏性刺激会激活中缝背核(DRN)中的血清素能神经元,而对DRN血清素能神经元进行光遗传学激活会诱发类似奖赏的效应。然而,血清素神经传递的药理学增强并不会诱发奖赏或厌恶效应。这些发现表明存在另一种血清素能神经元,它在处理奖赏和厌恶信息方面发挥着与DRN相反的作用。先前的报告表明中缝正中核(MRN)处理负面情绪刺激。为了阐明MRN血清素能神经元在这些过程中的功能,我们记录了小鼠血清素能活性对奖赏和厌恶刺激的反应变化。我们还使用光遗传学操作来确定这些变化是否会诱发奖赏和厌恶行为。MRN血清素能神经元的活性在对奖赏刺激的反应中降低,在厌恶刺激后增加。对MRN血清素能神经元的光遗传学抑制诱发了与奖赏相关的行为,而光遗传学刺激则诱发了与厌恶相关的行为。此外,我们发现从MRN血清素能神经元到脚间核的投射通路对这些过程至关重要。这些结果表明,MRN血清素能神经元在处理奖赏和厌恶信息方面起着关键作用,其功能与DRN神经元相反。