Dorsal raphe serotonergic neurons preferentially reactivate dorsal dentate gyrus cell ensembles associated with positive experience

被引:8
|
作者
Nagai, Yuma [1 ]
Kisaka, Yuri [1 ]
Nomura, Kento [1 ]
Nishitani, Naoya [2 ]
Andoh, Chihiro [1 ]
Koda, Masashi [1 ]
Kawai, Hiroyuki [1 ]
Seiriki, Kaoru [3 ]
Nagayasu, Kazuki [1 ]
Kasai, Atsushi [3 ]
Shirakawa, Hisashi [1 ]
Nakazawa, Takanobu [4 ]
Hashimoto, Hitoshi [3 ,5 ,6 ,7 ,8 ,9 ]
Kaneko, Shuji [1 ]
机构
[1] Kyoto Univ, Grad Sch Pharmaceut Sci, Dept Mol Pharmacol, 46-29 Yoshida Shimoadachi Cho,Sakyo Ku, Kyoto 6068501, Japan
[2] Kanazawa Univ, Inst Med Pharmaceut & Hlth Sci, Lab Mol Pharmacol, Kanazawa 9201192, Japan
[3] Osaka Univ, Grad Sch Pharmaceut Sci, Lab Mol Neuropharmacol, 1-6 Yamadaoka, Suita, Osaka 5650871, Japan
[4] Tokyo Univ Agr, Grad Sch Life Sci, Dept Biosci, Lab Mol Biol, 1-1-1 Sakuragaoka,Setagaya Ku, Tokyo 1568502, Japan
[5] Chiba Univ, Hamamatsu Univ Sch Med, Osaka Univ, Kanazawa Univ,United Grad Sch Child Dev,Mol Res Ct, 1-6 Yamadaoka, Suita, Osaka 5650871, Japan
[6] Univ Fukui, 1-6 Yamadaoka, Suita, Osaka 5650871, Japan
[7] Osaka Univ, Inst Databil Sci, Div Biosci, 1-1 Yamadaoka, Suita, Osaka 5650871, Japan
[8] Osaka Univ, Inst Open & Transdisciplinary Res Initiat, Transdimens Life Imaging Div, 2-1 Yamadaoka, Suita, Osaka 5650871, Japan
[9] Osaka Univ, Grad Sch Med, Dept Mol Pharmaceut Sci, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan
来源
CELL REPORTS | 2023年 / 42卷 / 03期
关键词
TRYPTOPHAN-HYDROXYLASE; DEPRESSION; STRESS; MEMORY; ANTIDEPRESSANT; CITALOPRAM; MEDIATE; FLUOXETINE; INHIBITORS; RECEPTORS;
D O I
10.1016/j.celrep.2023.112149
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Major depressive disorder (MDD) is among the most common mental illnesses. Serotonergic (5-HT) neurons are central to the pathophysiology and treatment of MDD. Repeatedly recalling positive episodes is effective for MDD. Stimulating 5-HT neurons of the dorsal raphe nucleus (DRN) or neuronal ensembles in the dorsal dentate gyrus (dDG) associated with positive memories reverses the stress-induced behavioral abnormal-ities. Despite this phenotypic similarity, their causal relationship is unclear. This study revealed that the DRN 5-HT neurons activate dDG neurons; surprisingly, this activation was specifically observed in positive memory ensembles rather than neutral or negative ensembles. Furthermore, we revealed that dopaminergic signaling induced by activation of DRN 5-HT neurons projecting to the ventral tegmental area mediates an increase in active coping behavior and positive dDG ensemble reactivation. Our study identifies a role of DRN 5-HT neurons as specific reactivators of positive memories and provides insights into how serotonin elicits antidepressive effects.
引用
收藏
页数:18
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