Laboratory/Faculty

G30 International Programs
Group of Genetic and Metabolic Regulation of Behavior

Designated ProfessorYoung-Jai You
Genetic and metabolic regulation of behavior
代謝が行動を調節する遺伝学的、神経学的機序の解明
▶Laboratory HP
Japanese
Young-Jai You Designated Professor
Lab members

Metabolic regulation of sleep

We spend almost one-third of our lives sleeping. Sleep deprivation contributes to decrease of productivity of an individual as well as of a society. Recent studies show sleep is evolutionarily conserved from jelly fish, worms, flies to mammals. Yet, why we sleep or how sleep is regulated are still largely unknown.

A circadian clock is a main controller of sleep timing. Interestingly, the clock can be entrained by food; if food is given only during the hours when the animals are supposed to sleep, they re-adjust their clock and stay awake during the feeding hours. In addition, orexin, a peptide hormone, regulates both sleep and feeding, suggesting feeding and sleep are closely linked.

We and others found that human sleep and C. elegans sleep are conserved both behaviorally and molecularly. In addition, we found that C. elegans shows a sleep-like state after feeding. Based on this discovery, we are investigating the molecular and neuronal mechanisms by which feeding and metabolism regulates sleep.

Metabolic regulation of feeding choice

Animals change their feeding choices based on the past experiences and nutritional or developmental needs. Hungry animals leave safety to seek food. Satiated animals stop seeking food and often sleep. Animals control feeding behavior by integrating multiple internal and external cues. Misregulation of this process causes several disorders from anorexia to obesity.

We study the feeding circuitry and molecular mechanisms by which multiple cues are integrated and the proper feeding behavior is chosen, using C. elegans. We have previously showed that C. elegans exhibits conserved hunger and satiety behaviors. In addition, we found that an aversive cue suppresses the sensation of a nutrient cue and hunger enhances the sensation of a nutrient cue. Based on these findings, we are investigating the neuro-molecular mechanisms underlying this switch. This branch of research will provide an insight into a fundamental question of how a brain makes a decision when conflicting cues are present.

Fig.1 How metabolism regulates sleep

A. We hypothesize feeding induces sleep via certain metabolites. The metabolites are produced after feeding, then act as ligands of nuclear receptors. Nuclear receptors are a group of transcription factors. Based on our recent studies regarding neouropeptides, we hypothesize the expression of specific neuropeptides are changed by nuclear receptors and as a result, control sleep.

B. To analyze the sleep and activities of an animal, we use our own built monitoring system and HMM based computer program. Using these tools, we can measure how much time an animal spends sleeping.


       A. The hypothesis and model        B. Tools to analyze the behavior

Fig.2 How metabolism regulates feeding choice

A-B. Two pairs of head sensory neurons respond to a nutrient cue(A:ASI neurons)and a noxious cue(B:ASH neurons).

C. When we give the animal mixed cues(nutrient and noxious together), the ASH suppresses ASI reponse to the nutrient cue.

D. We hypothesize that hungry animals would respond strongly to the nutrient cue and repress ASH activity. We suggest that this circuitry regulates the feeding choice depending on metabolic status of animals.

References

  1. 2018: Satiety behavior is regulated by ASI/ASH reciprocal antagonism. Davis KC, Choi YI, Kim J, You YJ. Sci Rep. 2018 May 2;8(1):6918.
    doi: 10.1038/s41598-018-24943-6.
  2. 2016: Fat Metabolism Regulates Satiety Behavior in C. elegans. Hyun M, Davis K, Lee I, Kim J, Dumur C, You YJ. Sci Rep. 2016 Apr 21;6:24841.
  3. 2015: An opioid-like system regulating feeding behavior in C. elegans. Cheong MC, Artyukhin AB, You YJ, Avery L. Elife. 2015 Apr 21;4.
  4. 2013: ASI regulates satiety quiescence in C. elegans. Gallagher T, Kim J, Oldenbroek M, Kerr R, You YJ. J Neurosci. 2013 Jun 5;33(23):9716-24
  5. 2008: Insulin, cGMP, and TGF-beta signals regulate food intake and quiescence in C. elegans: a model for satiety. You YJ, Kim J, Raizen DM, Avery L. Cell Metab. 2008 Mar;7(3):249-57
  6. 2008: Lethargus is a Caenorhabditis elegans sleep-like state. Raizen DM, Zimmerman JE, Maycock MH, Ta UD, You YJ, Sundaram MV, Pack AI. Nature. 2008 Jan 31;451(7178):569-72.
  7. 2006: Starvation activates MAP kinase through the muscarinic acetylcholine pathway in Caenorhabditis elegans pharynx. You YJ, Kim J, Cobb M, Avery L. Cell Metab. 2006 Apr;3(4):237-45

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