title: Dorsal raphe neurons signal reward through 5-HT and glutamate.
abstract: The dorsal raphe nucleus (DRN) in the midbrain is a key center for serotonin (5-hydroxytryptamine; 5-HT)-expressing neurons. Serotonergic neurons in the DRN have been theorized to encode punishment by opposing the reward signaling of dopamine neurons. Here, we show that DRN neurons encode reward, but not punishment, through 5-HT and glutamate. Optogenetic stimulation of DRN Pet-1 neurons reinforces mice to explore the stimulation-coupled spatial region, shifts sucrose preference, drives optical self-stimulation, and directs sensory discrimination learning. DRN Pet-1 neurons increase their firing activity during reward tasks, and this activation can be used to rapidly change neuronal activity patterns in the cortex. Although DRN Pet-1 neurons are often associated with 5-HT, they also release glutamate, and both neurotransmitters contribute to reward signaling. These experiments demonstrate the ability of DRN neurons to organize reward behaviors and might provide insights into the underlying mechanisms of learning facilitation and anhedonia treatment.
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China; College of Life Sciences, Beijing Normal University, Beijing 100875, China.
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China; PTN Graduate Program, School of Life Sciences, Peking University, Beijing 100081, China.
authors.forename: Jingfeng
authors.initials: J
authors.lastname: Zhou
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China; Graduate School of Peking Union Medical College, Beijing 100730, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China; Graduate School of Peking Union Medical College, Beijing 100730, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Hu
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Lu
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Ma
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Qiru
authors.initials: Q
authors.lastname: Feng
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China; School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Ju-En
authors.initials: JE
authors.lastname: Zhang
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China; School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Daqing
authors.initials: D
authors.lastname: Wang
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Zeng
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Junhong
authors.initials: J
authors.lastname: Bao
authors.affiliation: Center for the Study of Itch, and Departments of Anesthesiology, Psychiatry, and Developmental Biology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Center for the Study of Itch, and Departments of Anesthesiology, Psychiatry, and Developmental Biology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors.forename: Zhou-Feng
authors.initials: ZF
authors.lastname: Chen
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U952, 75005 Paris, France.
authors.forename: Salah
authors.initials: S
authors.lastname: El Mestikawy
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China; School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address: luominmin@nibs.ac.cn.
authors.forename: Minmin
authors.initials: M
authors.lastname: Luo
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism*; D008636:Mesencephalon / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism*; D011903:Raphe Nuclei / Q000378:metabolism; D012201:Reward; D012701:Serotonin / Q000378:metabolism*
chemical_list: D012701:Serotonin; D018698:Glutamic Acid