Dorsal Raphe Dual Serotonin-Glutamate Neurons Drive Reward by Establishing Excitatory Synapses on VTA Mesoaccumbens Dopamine Neurons
Summary: Dorsal raphe (DR) serotonin neurons provide a major input to the ventral tegmental area (VTA). Here, we show that DR serotonin transporter (SERT) neurons establish both asymmetric and symmetric synapses on VTA dopamine neurons, but most of these synapses are asymmetric. Moreover, the DR-SER...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-01-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719300221 |
| _version_ | 1819070652802400256 |
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| author | Hui-Ling Wang Shiliang Zhang Jia Qi Huikun Wang Roger Cachope Carlos A. Mejias-Aponte Jorge A. Gomez Gabriel E. Mateo-Semidey Gerard M.J. Beaudoin Carlos A. Paladini Joseph F. Cheer Marisela Morales |
| author_facet | Hui-Ling Wang Shiliang Zhang Jia Qi Huikun Wang Roger Cachope Carlos A. Mejias-Aponte Jorge A. Gomez Gabriel E. Mateo-Semidey Gerard M.J. Beaudoin Carlos A. Paladini Joseph F. Cheer Marisela Morales |
| author_sort | Hui-Ling Wang |
| collection | DOAJ |
| description | Summary: Dorsal raphe (DR) serotonin neurons provide a major input to the ventral tegmental area (VTA). Here, we show that DR serotonin transporter (SERT) neurons establish both asymmetric and symmetric synapses on VTA dopamine neurons, but most of these synapses are asymmetric. Moreover, the DR-SERT terminals making asymmetric synapses on VTA dopamine neurons coexpress vesicular glutamate transporter 3 (VGluT3; transporter for accumulation of glutamate for its synaptic release), suggesting the excitatory nature of these synapses. VTA photoactivation of DR-SERT fibers promotes conditioned place preference, elicits excitatory currents on mesoaccumbens dopamine neurons, increases their firing, and evokes dopamine release in nucleus accumbens. These effects are blocked by VTA inactivation of glutamate and serotonin receptors, supporting the idea of glutamate release in VTA from dual DR SERT-VGluT3 inputs. Our findings suggest a path-specific input from DR serotonergic neurons to VTA that promotes reward by the release of glutamate and activation of mesoaccumbens dopamine neurons. : Wang et al. identify the ultrastructural and molecular characteristics of synaptic connectivity between DR serotonin neurons and VTA dopamine neurons and determined the role of these connections in behavior. Their results indicate that the DR→VTA serotonergic neurons promote reward by the co-release of glutamate and activation of mesoaccumbens dopamine neurons. Keywords: dorsal raphe nucleus, ventral tegmental area, serotonin, VGluT3, reward |
| first_indexed | 2024-12-21T17:09:21Z |
| format | Article |
| id | doaj.art-defa00d29ee64dc08e3795bccabda37c |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-21T17:09:21Z |
| publishDate | 2019-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-defa00d29ee64dc08e3795bccabda37c2022-12-21T18:56:27ZengElsevierCell Reports2211-12472019-01-0126511281142.e7Dorsal Raphe Dual Serotonin-Glutamate Neurons Drive Reward by Establishing Excitatory Synapses on VTA Mesoaccumbens Dopamine NeuronsHui-Ling Wang0Shiliang Zhang1Jia Qi2Huikun Wang3Roger Cachope4Carlos A. Mejias-Aponte5Jorge A. Gomez6Gabriel E. Mateo-Semidey7Gerard M.J. Beaudoin8Carlos A. Paladini9Joseph F. Cheer10Marisela Morales11National Institute on Drug Abuse, Neuronal Networks Section, NIH, Baltimore, MD, USANational Institute on Drug Abuse, Electron Microscopy Core, NIH, Baltimore, MD, USANational Institute on Drug Abuse, Neuronal Networks Section, NIH, Baltimore, MD, USANational Institute on Drug Abuse, Neuronal Networks Section, NIH, Baltimore, MD, USADepartment of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USANational Institute on Drug Abuse, Neuronal Networks Section, NIH, Baltimore, MD, USADepartment of Biology, University of Texas at San Antonio, San Antonio, TX, USANational Institute on Drug Abuse, Neuronal Networks Section, NIH, Baltimore, MD, USADepartment of Biology, University of Texas at San Antonio, San Antonio, TX, USADepartment of Biology, University of Texas at San Antonio, San Antonio, TX, USADepartment of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USANational Institute on Drug Abuse, Neuronal Networks Section, NIH, Baltimore, MD, USA; Corresponding authorSummary: Dorsal raphe (DR) serotonin neurons provide a major input to the ventral tegmental area (VTA). Here, we show that DR serotonin transporter (SERT) neurons establish both asymmetric and symmetric synapses on VTA dopamine neurons, but most of these synapses are asymmetric. Moreover, the DR-SERT terminals making asymmetric synapses on VTA dopamine neurons coexpress vesicular glutamate transporter 3 (VGluT3; transporter for accumulation of glutamate for its synaptic release), suggesting the excitatory nature of these synapses. VTA photoactivation of DR-SERT fibers promotes conditioned place preference, elicits excitatory currents on mesoaccumbens dopamine neurons, increases their firing, and evokes dopamine release in nucleus accumbens. These effects are blocked by VTA inactivation of glutamate and serotonin receptors, supporting the idea of glutamate release in VTA from dual DR SERT-VGluT3 inputs. Our findings suggest a path-specific input from DR serotonergic neurons to VTA that promotes reward by the release of glutamate and activation of mesoaccumbens dopamine neurons. : Wang et al. identify the ultrastructural and molecular characteristics of synaptic connectivity between DR serotonin neurons and VTA dopamine neurons and determined the role of these connections in behavior. Their results indicate that the DR→VTA serotonergic neurons promote reward by the co-release of glutamate and activation of mesoaccumbens dopamine neurons. Keywords: dorsal raphe nucleus, ventral tegmental area, serotonin, VGluT3, rewardhttp://www.sciencedirect.com/science/article/pii/S2211124719300221 |
| spellingShingle | Hui-Ling Wang Shiliang Zhang Jia Qi Huikun Wang Roger Cachope Carlos A. Mejias-Aponte Jorge A. Gomez Gabriel E. Mateo-Semidey Gerard M.J. Beaudoin Carlos A. Paladini Joseph F. Cheer Marisela Morales Dorsal Raphe Dual Serotonin-Glutamate Neurons Drive Reward by Establishing Excitatory Synapses on VTA Mesoaccumbens Dopamine Neurons Cell Reports |
| title | Dorsal Raphe Dual Serotonin-Glutamate Neurons Drive Reward by Establishing Excitatory Synapses on VTA Mesoaccumbens Dopamine Neurons |
| title_full | Dorsal Raphe Dual Serotonin-Glutamate Neurons Drive Reward by Establishing Excitatory Synapses on VTA Mesoaccumbens Dopamine Neurons |
| title_fullStr | Dorsal Raphe Dual Serotonin-Glutamate Neurons Drive Reward by Establishing Excitatory Synapses on VTA Mesoaccumbens Dopamine Neurons |
| title_full_unstemmed | Dorsal Raphe Dual Serotonin-Glutamate Neurons Drive Reward by Establishing Excitatory Synapses on VTA Mesoaccumbens Dopamine Neurons |
| title_short | Dorsal Raphe Dual Serotonin-Glutamate Neurons Drive Reward by Establishing Excitatory Synapses on VTA Mesoaccumbens Dopamine Neurons |
| title_sort | dorsal raphe dual serotonin glutamate neurons drive reward by establishing excitatory synapses on vta mesoaccumbens dopamine neurons |
| url | http://www.sciencedirect.com/science/article/pii/S2211124719300221 |
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