TY - JOUR
T1 - Median raphe serotonergic neurons projecting to the interpeduncular nucleus control preference and aversion
AU - Kawai, Hiroyuki
AU - Bouchekioua, Youcef
AU - Nishitani, Naoya
AU - Niitani, Kazuhei
AU - Izumi, Shoma
AU - Morishita, Hinako
AU - Andoh, Chihiro
AU - Nagai, Yuma
AU - Koda, Masashi
AU - Hagiwara, Masako
AU - Toda, Koji
AU - Shirakawa, Hisashi
AU - Nagayasu, Kazuki
AU - Ohmura, Yu
AU - Kondo, Makoto
AU - Kaneda, Katsuyuki
AU - Yoshioka, Mitsuhiro
AU - Kaneko, Shuji
N1 - Funding Information:
We would like to thank Dr. Hiroyuki Hasegawa for kindly gifting us anti-tryptophan hydroxylase 2 antibodies. We would like to thank Drs. Akihiro Yamanaka and Kenji F. Tanaka for kindly providing us with Tph2-tTA and TetO-ChR2(C128S) mice. We would like to thank Dr. Hitomi Sasamori for her help in the breeding of transgenic mice. We would like to thank Drs. Mike Robinson and Kent Berridge for telling us how to conduct the surgery of oral infusion. We would like to thank Hitoshi Saito for his help in programming. We would like to thank Dr. Masaaki Sato for kindly lending us an infusion pump. We would like to thank Drs. Katsuyuki Kaneda and Satoshi Deyama for help on the CPP/CPA tests. We would like to thank Drs. Atsushi Miyawaki (pCSII-EF-Venus), Adam Cohen (CheRiff; addgene #51694), Karl Deisseroth (eArchT; addgene #35513), Douglas Kim and GENIE Project (GCaMP6s; addgene #40753), and Lin Tian (axon-GCaMP6s; addgene #112008) for providing us the constructs. This work was supported by Grants-in-Aid for Scientific Research from JSPS (to K.Nagayasu (JP20H04774, JP20K07064), to S.K. (JP18H04616, JP20H00491), to Y.O. (21K07473), to M.Y. (21H02668), to M.Kondo (JP22K11498), Grant-in-Aid for Nagai Memorial Research Scholarship from the Pharmaceutical Society of Japan (to H.K. (N-184403)), Grants-in-Aid for JSPS Fellows (to H.K. (JP20J12341), Y.N. (JP21J14215), and C.A. (JP21J21091)), AMED (to S.K. (JP20ak0101088h0003, JP21ak0101153h0001), to M.Kondo (JP21wm0525026, JP20lm0203007)), Smoking Research Foundation (to Y.O.), The Shimizu Foundation for Immunology and Neuroscience Grant (to K.Nagayasu), The Uehara Memorial Foundation (to K.Nagayasu), The Lotte Foundation (to K.Nagayasu), Takeda Science Foundation (to M.Kondo), SENSHIN Medical Research Foundation (M.Kondo).
Funding Information:
We would like to thank Dr. Hiroyuki Hasegawa for kindly gifting us anti-tryptophan hydroxylase 2 antibodies. We would like to thank Drs. Akihiro Yamanaka and Kenji F. Tanaka for kindly providing us with Tph2-tTA and TetO-ChR2(C128S) mice. We would like to thank Dr. Hitomi Sasamori for her help in the breeding of transgenic mice. We would like to thank Drs. Mike Robinson and Kent Berridge for telling us how to conduct the surgery of oral infusion. We would like to thank Hitoshi Saito for his help in programming. We would like to thank Dr. Masaaki Sato for kindly lending us an infusion pump. We would like to thank Drs. Katsuyuki Kaneda and Satoshi Deyama for help on the CPP/CPA tests. We would like to thank Drs. Atsushi Miyawaki (pCSII-EF-Venus), Adam Cohen (CheRiff; addgene #51694), Karl Deisseroth (eArchT; addgene #35513), Douglas Kim and GENIE Project (GCaMP6s; addgene #40753), and Lin Tian (axon-GCaMP6s; addgene #112008) for providing us the constructs. This work was supported by Grants-in-Aid for Scientific Research from JSPS (to K.Nagayasu (JP20H04774, JP20K07064), to S.K. (JP18H04616, JP20H00491), to Y.O. (21K07473), to M.Y. (21H02668), to M.Kondo (JP22K11498), Grant-in-Aid for Nagai Memorial Research Scholarship from the Pharmaceutical Society of Japan (to H.K. (N-184403)), Grants-in-Aid for JSPS Fellows (to H.K. (JP20J12341), Y.N. (JP21J14215), and C.A. (JP21J21091)), AMED (to S.K. (JP20ak0101088h0003, JP21ak0101153h0001), to M.Kondo (JP21wm0525026, JP20lm0203007)), Smoking Research Foundation (to Y.O.), The Shimizu Foundation for Immunology and Neuroscience Grant (to K.Nagayasu), The Uehara Memorial Foundation (to K.Nagayasu), The Lotte Foundation (to K.Nagayasu), Takeda Science Foundation (to M.Kondo), SENSHIN Medical Research Foundation (M.Kondo).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-022-35346-7
DO - 10.1038/s41467-022-35346-7
M3 - Article
C2 - 36550097
AN - SCOPUS:85144545926
SN - 2041-1723
VL - 13
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 7708
ER -