Median raphe serotonergic neurons projecting to the interpeduncular nucleus control preference and aversion

Hiroyuki Kawai, Youcef Bouchekioua, Naoya Nishitani, Kazuhei Niitani, Shoma Izumi, Hinako Morishita, Chihiro Andoh, Yuma Nagai, Masashi Koda, Masako Hagiwara, Koji Toda, Hisashi Shirakawa, Kazuki Nagayasu (), Yu Ohmura (), Makoto Kondo, Katsuyuki Kaneda, Mitsuhiro Yoshioka and Shuji Kaneko ()
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Hiroyuki Kawai: Kyoto University
Youcef Bouchekioua: Hokkaido University
Naoya Nishitani: Kyoto University
Kazuhei Niitani: Kanazawa University
Shoma Izumi: Kanazawa University
Hinako Morishita: Kyoto University
Chihiro Andoh: Kyoto University
Yuma Nagai: Kyoto University
Masashi Koda: Kyoto University
Masako Hagiwara: Kyoto University
Koji Toda: Keio University
Hisashi Shirakawa: Kyoto University
Kazuki Nagayasu: Kyoto University
Yu Ohmura: Hokkaido University
Makoto Kondo: Osaka Metropolitan University
Katsuyuki Kaneda: Kanazawa University
Mitsuhiro Yoshioka: Hokkaido University
Shuji Kaneko: Kyoto University

Nature Communications, 2022, vol. 13, issue 1, 1-22

Abstract: Abstract 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-HTMRN→IPN), as a key mediator of reward and aversive stimuli. Moreover, 5-HT receptors, including 5-HT2A 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-HTMRN→IPN, in the processing of reward and aversive stimuli.

Date: 2022
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DOI: 10.1038/s41467-022-35346-7

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