Cover Story Current Issue

Consuming small amounts of palatable food, i.e., snacking, at various times of the day is a highly prevalent behavior in most modern societies. Chronic rest-phase food intake – especially of high-caloric items – promotes obesity and disrupts endogenous circadian rhythms. Notably, humans and mice are more prone to hedonically driven eating behavior, the overconsumption of palatable food, during the late active/early inactive phase, i.e., the morning in mice, the evening in humans. While the effects of calorie-dense food items in promoting body weight gain are well documented, the metabolic impact of snack timing is far less understood.

Kimberly Begemann, Isabel Heyde, Pia Witt, Julica Inderhees, ... Henrik Oster

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Current Issue

Dorsal raphe serotonergic neurons suppress feeding through redundant forebrain circuits

Iltan Aklan, Nilufer Sayar-Atasoy, Fei Deng, Hyojin Kim, ... Deniz Atasoy

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 → LHvGlut2connections 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 DRN5HTneurons suppress feeding and reveal that these projections can be modulated by metabolic hormones.

     

 

Articles in Press

Dorsal raphe serotonergic neurons suppress feeding through redundant forebrain circuits

Iltan Aklan, Nilufer Sayar-Atasoy, Fei Deng, Hyojin Kim, ... Deniz Atasoy

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 → LHvGlut2connections 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 DRN5HTneurons suppress feeding and reveal that these projections can be modulated by metabolic hormones.

     

 

2021 impact factor: 8.568

You are what you eat

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