Dorsal Raphe Serotonergic Neurons Suppress Feeding Through Redundant Forebrain Circuits

Iltan Aklan; Nilufer Sayar Atasoy; Fei Deng; Hyojin Kim; Yavuz Yavuz; Jacob Rysted; Connor Laule; Debbie Davis; Yulong Li; Deniz Atasoy

doi:10.1016/j.molmet.2023.101676

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Dorsal Raphe Serotonergic Neurons Suppress Feeding Through Redundant Forebrain Circuits

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Dorsal Raphe Serotonergic Neurons Suppress Feeding Through Redundant Forebrain Circuits

Iltan Aklan, Nilufer Sayar Atasoy, Fei Deng, Hyojin Kim, Yavuz Yavuz, Jacob Rysted, Connor Laule, Debbie Davis, Yulong Li and Deniz Atasoy

Molecular metabolism (Germany), Vol.60, 101676

01/19/2023

DOI: 10.1016/j.molmet.2023.101676

PMCID: PMC9923194

PMID: 36682413

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Abstract

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.

Details

Title: Subtitle: Dorsal Raphe Serotonergic Neurons Suppress Feeding Through Redundant Forebrain Circuits
Creators: Iltan Aklan - Department of Neuroscience and Pharmacology
Nilufer Sayar Atasoy - Department of Neuroscience and Pharmacology
Fei Deng - Peking University
Hyojin Kim - Department of Neuroscience and Pharmacology
Yavuz Yavuz
Jacob Rysted - Department of Neuroscience and Pharmacology
Connor Laule - Department of Neuroscience and Pharmacology
Debbie Davis - Department of Neuroscience and Pharmacology
Yulong Li - Iowa Neuroscience Institute
Deniz Atasoy
Resource Type: Journal article
Publication Details: Molecular metabolism (Germany), Vol.60, 101676
DOI: 10.1016/j.molmet.2023.101676
PMID: 36682413
PMCID: PMC9923194
NLM abbreviation: Mol Metab
ISSN: 2212-8778
eISSN: 2212-8778
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health, award: R01DK126740
Language: English
Date published: 01/19/2023
Academic Unit: Neurology; Pathology; Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology
Record Identifier: 9984362757902771

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