Dorsal raphe serotonergic neurons suppress feeding through redundant forebrain circuits
Objective: Serotonin (5HT) is a well-known anorexigenic molecule, and 5HT neurons of dorsal raphe nucleus (DRN) have been implicated in suppression of feeding; however, the downstream circuitry is poorly understood. Here we explored major projections of DRN5HT neurons for their capacity to modulate...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | Molecular Metabolism |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877823000108 |
| _version_ | 1797893752366301184 |
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| author | Iltan Aklan Nilufer Sayar-Atasoy Fei Deng Hyojin Kim Yavuz Yavuz Jacob Rysted Connor Laule Debbie Davis Yulong Li Deniz Atasoy |
| author_facet | Iltan Aklan Nilufer Sayar-Atasoy Fei Deng Hyojin Kim Yavuz Yavuz Jacob Rysted Connor Laule Debbie Davis Yulong Li Deniz Atasoy |
| author_sort | Iltan Aklan |
| collection | DOAJ |
| description | Objective: Serotonin (5HT) is a well-known anorexigenic molecule, and 5HT neurons of dorsal raphe nucleus (DRN) have been implicated in suppression of feeding; however, the downstream circuitry is poorly understood. Here we explored major projections of DRN5HT neurons for their capacity to modulate feeding. Methods: We used optogenetics to selectively activate DRN5HT axonal projections in hypothalamic and extrahypothalamic areas and monitored food intake. We next used fiber photometry to image the activity dynamics of DRN5HT axons and 5HT levels in projection areas in response feeding and metabolic hormones. Finally, we used electrophysiology to determine how DRN5HT axons affect downstream neuron activity. Results: We found that selective activation of DRN5HT axons in (DRN5HT → LH) and (DRN5HT → BNST) suppresses feeding whereas activating medial hypothalamic projections has no effect. Using in vivo imaging, we found that food access and satiety hormones activate DRN5HT projections to LH where they also rapidly increase extracellular 5HT levels. Optogenetic mapping revealed that DRN5HT → LHvGAT and DRN5HT → LHvGlut2 connections are primarily inhibitory and excitatory respectively. Further, in addition to its direct action on LH neurons, we found that 5HT suppresses GABA release from presynaptic terminals arriving from AgRP neurons. Conclusions: These findings define functionally redundant forebrain circuits through which DRN5HT neurons suppress feeding and reveal that these projections can be modulated by metabolic hormones. |
| first_indexed | 2024-04-10T06:59:06Z |
| format | Article |
| id | doaj.art-10b3c24e4b8043df87ea5ffe937095fa |
| institution | Directory Open Access Journal |
| issn | 2212-8778 |
| language | English |
| last_indexed | 2024-04-10T06:59:06Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj.art-10b3c24e4b8043df87ea5ffe937095fa2023-02-28T04:08:46ZengElsevierMolecular Metabolism2212-87782023-03-0169101676Dorsal raphe serotonergic neurons suppress feeding through redundant forebrain circuitsIltan Aklan0Nilufer Sayar-Atasoy1Fei Deng2Hyojin Kim3Yavuz Yavuz4Jacob Rysted5Connor Laule6Debbie Davis7Yulong Li8Deniz Atasoy9Department of Neuroscience and Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USADepartment of Neuroscience and Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USAState Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing 100871, ChinaDepartment of Neuroscience and Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USADepartment of Neuroscience and Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA; Department of Physiology, School of Medicine, Yeditepe University, Istanbul, TurkeyDepartment of Neuroscience and Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USADepartment of Neuroscience and Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USADepartment of Neuroscience and Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USAState Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing 100871, ChinaDepartment of Neuroscience and Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA; Iowa Neuroscience Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA; Fraternal Order of Eagles Diabetes Research Center (FOEDRC), Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA; Corresponding author. Department of Pharmacology, Carver College of Medicine, University of Iowa, 51 Newton Rd, Iowa City, IA 52242, USA. Fax: +1 319 335 8930.Objective: Serotonin (5HT) is a well-known anorexigenic molecule, and 5HT neurons of dorsal raphe nucleus (DRN) have been implicated in suppression of feeding; however, the downstream circuitry is poorly understood. Here we explored major projections of DRN5HT neurons for their capacity to modulate feeding. Methods: We used optogenetics to selectively activate DRN5HT axonal projections in hypothalamic and extrahypothalamic areas and monitored food intake. We next used fiber photometry to image the activity dynamics of DRN5HT axons and 5HT levels in projection areas in response feeding and metabolic hormones. Finally, we used electrophysiology to determine how DRN5HT axons affect downstream neuron activity. Results: We found that selective activation of DRN5HT axons in (DRN5HT → LH) and (DRN5HT → BNST) suppresses feeding whereas activating medial hypothalamic projections has no effect. Using in vivo imaging, we found that food access and satiety hormones activate DRN5HT projections to LH where they also rapidly increase extracellular 5HT levels. Optogenetic mapping revealed that DRN5HT → LHvGAT and DRN5HT → LHvGlut2 connections are primarily inhibitory and excitatory respectively. Further, in addition to its direct action on LH neurons, we found that 5HT suppresses GABA release from presynaptic terminals arriving from AgRP neurons. Conclusions: These findings define functionally redundant forebrain circuits through which DRN5HT neurons suppress feeding and reveal that these projections can be modulated by metabolic hormones.http://www.sciencedirect.com/science/article/pii/S2212877823000108Serotonin5HTFeedingDorsal rapheSatiety |
| spellingShingle | Iltan Aklan Nilufer Sayar-Atasoy Fei Deng Hyojin Kim Yavuz Yavuz Jacob Rysted Connor Laule Debbie Davis Yulong Li Deniz Atasoy Dorsal raphe serotonergic neurons suppress feeding through redundant forebrain circuits Molecular Metabolism Serotonin 5HT Feeding Dorsal raphe Satiety |
| title | Dorsal raphe serotonergic neurons suppress feeding through redundant forebrain circuits |
| title_full | Dorsal raphe serotonergic neurons suppress feeding through redundant forebrain circuits |
| title_fullStr | Dorsal raphe serotonergic neurons suppress feeding through redundant forebrain circuits |
| title_full_unstemmed | Dorsal raphe serotonergic neurons suppress feeding through redundant forebrain circuits |
| title_short | Dorsal raphe serotonergic neurons suppress feeding through redundant forebrain circuits |
| title_sort | dorsal raphe serotonergic neurons suppress feeding through redundant forebrain circuits |
| topic | Serotonin 5HT Feeding Dorsal raphe Satiety |
| url | http://www.sciencedirect.com/science/article/pii/S2212877823000108 |
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